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39 60 peptide binding‐motif structure_element Structure‐activity relationship of the peptide binding‐motif mediating the BRCA2:RAD51 protein–protein interaction TITLE |
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75 86 BRCA2:RAD51 complex_assembly Structure‐activity relationship of the peptide binding‐motif mediating the BRCA2:RAD51 protein–protein interaction TITLE |
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1 6 RAD51 protein RAD51 is a recombinase involved in the homologous recombination of double‐strand breaks in DNA. ABSTRACT |
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12 23 recombinase protein_type RAD51 is a recombinase involved in the homologous recombination of double‐strand breaks in DNA. ABSTRACT |
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0 5 RAD51 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT |
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12 21 oligomers oligomeric_state RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT |
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56 61 RAD51 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT |
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70 74 FxxA structure_element RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT |
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147 152 BRCA2 protein RAD51 forms oligomers by binding to another molecule of RAD51 via an ‘FxxA’ motif, and the same recognition sequence is similarly utilised to bind BRCA2. ABSTRACT |
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33 41 mutation experimental_method We have tabulated the effects of mutation of this sequence, across a variety of experimental methods and from relevant mutations observed in the clinic. ABSTRACT |
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7 14 mutants protein_state We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT |
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20 32 tetrapeptide chemical We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT |
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87 119 isothermal titration calorimetry experimental_method We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT |
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124 145 X‐ray crystallography experimental_method We use mutants of a tetrapeptide sequence to probe the binding interaction, using both isothermal titration calorimetry and X‐ray crystallography. ABSTRACT |
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39 68 tetrapeptide mutational study experimental_method Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered. ABSTRACT |
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202 218 alanine scanning experimental_method Where possible, comparison between our tetrapeptide mutational study and the previously reported mutations is made, discrepancies are discussed and the importance of secondary structure in interpreting alanine scanning and mutational data of this nature is considered. ABSTRACT |
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0 10 Eukaryotic taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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11 16 RAD51 protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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18 25 archeal taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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26 30 RadA protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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35 46 prokaryotic taxonomy_domain Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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47 51 RecA protein Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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68 94 ATP‐dependent recombinases protein_type Eukaryotic RAD51, archeal RadA and prokaryotic RecA are a family of ATP‐dependent recombinases involved in homologous recombination (HR) of double‐strand breaks in DNA 1. ABBR |
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0 5 RAD51 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR |
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21 26 BRCA2 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR |
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55 60 RAD51 protein RAD51 interacts with BRCA2, and is thought to localise RAD51 to sites of DNA damage 2, 3. ABBR |
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5 10 BRCA2 protein Both BRCA2 and RAD51 together are vital for helping to repair and maintain a high fidelity in DNA replication. ABBR |
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15 20 RAD51 protein Both BRCA2 and RAD51 together are vital for helping to repair and maintain a high fidelity in DNA replication. ABBR |
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0 5 BRCA2 protein BRCA2 especially has garnered much attention in a clinical context, as many mutations have been identified that drive an increased risk of cancer in individuals 4, 5. ABBR |
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33 44 BRCA2:RAD51 complex_assembly Although the inactivation of the BRCA2:RAD51 DNA repair pathway can cause genomic instability and eventual tumour development, an inability to repair breaks in DNA may also engender a sensitivity to ionising radiation 6, 7. ABBR |
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71 82 BRCA2:RAD51 complex_assembly For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR |
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153 158 RAD51 protein For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR |
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163 168 BRCA2 protein For this reason it is hypothesised that in tumour cells with an intact BRCA2:RAD51 repair pathway, small molecules which prevent the interaction between RAD51 and BRCA2 may confer radiosensitivity by disabling the HR pathway 8. ABBR |
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62 73 BRC repeats structure_element The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR |
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104 113 conserved protein_state The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR |
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114 128 ‘FxxA’ motif 9 structure_element The interaction between the two proteins is mediated by eight BRC repeats, which are characterised by a conserved ‘FxxA’ motif 9. ABBR |
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0 5 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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10 14 RadA protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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41 45 FxxA structure_element RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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57 61 FTTA structure_element RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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66 71 human species RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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72 77 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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114 119 RAD51 protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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124 128 RadA protein RAD51 and RadA proteins also contain an ‘FxxA’ sequence (FTTA for human RAD51) through which it can bind to other RAD51 and RadA molecules, and oligomerise to form higher order filament structures on DNA. ABBR |
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11 15 FxxA structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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35 46 BRC repeats structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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51 56 RAD51 protein The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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57 81 oligomerisation sequence structure_element The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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109 126 FxxA‐binding site site The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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130 135 RAD51 protein The common FxxA motifs of both the BRC repeats and RAD51 oligomerisation sequence are recognised by the same FxxA‐binding site of RAD51. ABBR |
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73 87 binding energy evidence In general, the dominant contribution of certain residues to the overall binding energy of a protein–protein interaction are known as ‘hot‐spot’ residues. ABBR |
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135 143 hot‐spot site In general, the dominant contribution of certain residues to the overall binding energy of a protein–protein interaction are known as ‘hot‐spot’ residues. ABBR |
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84 91 pockets site Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR |
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124 132 hot‐spot site Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR |
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149 155 native protein_state Interestingly, small molecule inhibitors of PPIs are often found to occupy the same pockets which are otherwise occupied by hot‐spot residues in the native complex. ABBR |
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46 55 hot‐spots site It is therefore of great interest to identify hot‐spots in an effort to guide drug discovery efforts against a PPI. ABBR |
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49 67 strongly conserved protein_state Further, a correlation between residues that are strongly conserved and hot‐spot residues has been reported 10. ABBR |
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72 80 hot‐spot site Further, a correlation between residues that are strongly conserved and hot‐spot residues has been reported 10. ABBR |
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84 97 phenylalanine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR |
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102 109 alanine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR |
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139 148 hot‐spots site Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR |
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173 182 threonine residue_name Purely based on the amino acid consensus sequence reported by Pellegrini et al., 11 phenylalanine and alanine would both be expected to be hot‐spots and to a lesser extent, threonine. ABBR |
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38 54 highly conserved protein_state However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR |
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109 118 hot‐spots site However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR |
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147 155 mutation experimental_method However, whilst the identification of highly conserved residues may be a good starting point for identifying hot‐spots, experimental validation by mutation of these sequences is vital. ABBR |
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34 38 FxxA structure_element The importance of residues in the FxxA motif has been probed by a variety of techniques, collated in Table 1. ABBR |
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9 17 mutating experimental_method Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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18 31 phenylalanine residue_name Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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35 48 glutamic acid residue_name Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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49 60 inactivated protein_state Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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65 69 BRC4 chemical Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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92 97 RAD51 protein Briefly, mutating phenylalanine to glutamic acid inactivated the BRC4 peptide and prevented RAD51 oligomerisation 11, 12. ABBR |
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2 25 phenylalanine‐truncated protein_state A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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26 30 BRC4 chemical A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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51 59 inactive protein_state A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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73 84 introducing experimental_method A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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87 97 tryptophan residue_name A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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102 115 phenylalanine residue_name A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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159 163 BRC4 chemical A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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164 172 affinity evidence A phenylalanine‐truncated BRC4 is also found to be inactive 13, however, introducing a tryptophan for phenylalanine was found to have no significant effect on BRC4 affinity 12. ABBR |
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2 11 glutamine residue_name A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR |
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12 21 replacing experimental_method A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR |
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26 35 histidine residue_name A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR |
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39 43 BRC4 chemical A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR |
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54 58 BRC4 chemical A glutamine replacing the histidine in BRC4 maintains BRC4 activity 13. ABBR |
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15 19 BRC3 chemical The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR |
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37 42 RAD51 protein The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR |
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85 94 threonine residue_name The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR |
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98 105 mutated experimental_method The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR |
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112 119 alanine residue_name The ability of BRC3 to interact with RAD51 nucleoprotein filaments is disrupted when threonine is mutated to an alanine 3. ABBR |
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11 19 mutating experimental_method Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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20 27 alanine residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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31 44 glutamic acid residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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52 57 RAD51 protein Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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58 82 oligomerisation sequence structure_element Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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92 98 serine residue_name Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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102 106 BRC4 chemical Similarly, mutating alanine to glutamic acid in the RAD51 oligomerisation sequence 11 or to serine in BRC4 13 leads to loss of interaction in both cases. ABBR |
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4 8 BRC5 chemical The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR |
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19 25 humans species The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR |
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30 36 serine residue_name The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR |
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53 60 alanine residue_name The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR |
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85 102 nonbinding repeat structure_element The BRC5 repeat in humans has serine in the place of alanine, and is thought to be a nonbinding repeat 12. ABBR |
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43 47 FxxA structure_element Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR |
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62 73 BRC repeats structure_element Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR |
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77 82 BRCA2 protein Mutations identified in the clinic, in the FxxA region of the BRC repeats of BRCA2 are collated in Table 1 14. ABBR |
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163 168 RAD51 protein For completeness, we present them here with this caveat, and to make the comment that these clinical mutations are consistent with abrogating the interaction with RAD51. ABBR |
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11 15 FxxA structure_element Summary of FxxA‐relevant mutations previously reported and degree of characterisation. TABLE |
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50 54 FxxA structure_element The mutation, relevant peptide context, resulting FxxA motif sequence and experimental technique for each entry is given. TABLE |
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27 31 FxxA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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62 67 RAD51 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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69 73 FTTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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75 79 F86E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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80 84 ETTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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85 104 Immunoprecipitation experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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121 125 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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127 131 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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133 139 F1524E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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140 144 EHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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145 162 Competitive ELISA experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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174 182 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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185 189 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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191 195 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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197 203 F1524W mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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204 208 WHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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209 226 Competitive ELISA experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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253 255 WT protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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258 262 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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264 268 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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270 276 F1524V mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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277 281 VHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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282 287 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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314 318 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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320 324 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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326 332 ΔF1524 mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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334 337 HTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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354 363 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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383 391 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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394 398 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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400 404 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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406 412 H1525Q mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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413 417 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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434 443 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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477 481 BRC7 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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483 487 FSTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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489 495 S1979R mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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496 500 FRTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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501 506 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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533 537 BRC3 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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539 543 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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545 551 T1430A mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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552 556 FQAA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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557 566 RAD51:DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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567 582 bandshift assay experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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593 601 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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604 608 BRC3 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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610 614 FQTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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616 622 T1430A mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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623 627 FQAA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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628 648 Electron microscopic experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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700 708 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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711 715 BRC1 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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717 721 FRTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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723 729 T1011R mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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730 734 FRRA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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735 740 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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767 771 BRC2 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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773 777 FYSA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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779 785 S1221P mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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786 790 FYPA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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791 796 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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823 827 BRC2 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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829 833 FYSA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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835 841 S1221Y mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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842 846 FYYA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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847 852 BRCA2 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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879 884 RAD51 protein "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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886 890 FTTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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892 896 A89E mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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897 901 FTTE structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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902 921 Immunoprecipitation experimental_method "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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938 942 BRC4 chemical "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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944 948 FHTA structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
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950 956 A1527S mutant "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
|
957 961 FHTS structure_element "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
|
978 987 RAD51‐DNA complex_assembly "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
|
1007 1015 inactive protein_state "Mutation contexta Mutation FxxA motif Technique used Effect RAD51 (FTTA) F86E ETTA Immunoprecipitation 11 No binding BRC4 (FHTA) F1524E EHTA Competitive ELISA 12 Peptide inactive BRC4 (FHTA) F1524W WHTA Competitive ELISA 12 Comparable activity to WT BRC4 (FHTA) F1524V VHTA BRCA2 mutations database 14 – BRC4 (FHTA) ΔF1524 ‐HTA Dissociation of RAD51‐DNA complex 13 Peptide inactive BRC4 (FHTA) H1525Q FQTA Dissociation of RAD51‐DNA complex 13 Comparable activity BRC7 (FSTA) S1979R FRTA BRCA2 mutations database 14 – BRC3 (FQTA) T1430A FQAA RAD51:DNA bandshift assay 3 Peptide inactive BRC3 (FQTA) T1430A FQAA Electron microscopic visualisation of nucleoprotein filaments 3 Peptide inactive BRC1 (FRTA) T1011R FRRA BRCA2 mutations database 14 – BRC2 (FYSA) S1221P FYPA BRCA2 mutations database 14 – BRC2 (FYSA) S1221Y FYYA BRCA2 mutations database 14 – RAD51 (FTTA) A89E FTTE Immunoprecipitation 11 No binding BRC4 (FHTA) A1527S FHTS Dissociation of RAD51‐DNA complex 13 Peptide inactive " TABLE |
|
4 13 wild‐type protein_state The wild‐type FxxA sequence is indicated in parenthesis. TABLE |
|
14 18 FxxA structure_element The wild‐type FxxA sequence is indicated in parenthesis. TABLE |
|
51 71 systematic mutations experimental_method In this work, we report the most detailed study of systematic mutations of peptides to probe the FxxA‐binding motif to date. ABBR |
|
97 115 FxxA‐binding motif structure_element In this work, we report the most detailed study of systematic mutations of peptides to probe the FxxA‐binding motif to date. ABBR |
|
27 40 tetrapeptides chemical We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR |
|
83 91 mutation experimental_method We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR |
|
128 132 FxxA structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR |
|
175 185 BRC repeat structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR |
|
189 218 self‐oligomerisation sequence structure_element We have chosen to focus on tetrapeptides, which allows us to examine the effect of mutation on the fundamental unit of binding, FxxA, rather than in the context of either the BRC repeat or self‐oligomerisation sequence. ABBR |
|
0 10 Affinities evidence Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
52 84 Isothermal Titration Calorimetry experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
86 89 ITC experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
99 109 structures evidence Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
134 142 bound to protein_state Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
143 152 humanised protein_state Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
153 157 RadA protein Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
177 198 X‐ray crystallography experimental_method Affinities of peptides were measured directly using Isothermal Titration Calorimetry (ITC) and the structures of many of the peptides bound to humanised RadA were determined by X‐ray crystallography. ABBR |
|
11 14 ITC experimental_method The use of ITC is generally perceived as a gold‐standard in protein–ligand characterisation, rather than a competitive assay which may be prone to aggregation artefacts. ABBR |
|
107 124 competitive assay experimental_method The use of ITC is generally perceived as a gold‐standard in protein–ligand characterisation, rather than a competitive assay which may be prone to aggregation artefacts. ABBR |
|
0 9 Wild‐type protein_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
10 15 human species Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
16 21 RAD51 protein Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
62 71 oligomers oligomeric_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
81 92 monomerised oligomeric_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
96 104 mutation experimental_method Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
109 124 highly unstable protein_state Wild‐type human RAD51, however, is a heterogeneous mixture of oligomers and when monomerised by mutation, is highly unstable. ABBR |
|
56 62 stable protein_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
63 72 monomeric oligomeric_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
82 87 RAD51 protein In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
89 98 humanised protein_state In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
104 123 Pyrococcus furiosus species In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
134 138 RadA protein In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
144 147 ITC experimental_method In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
164 185 X‐ray crystallography experimental_method In this context, we have previously reported the use of stable monomeric forms of RAD51, humanised from Pyrococcus furiosus homologue RadA, for ITC experiments and X‐ray crystallography 8, 15. ABBR |
|
16 20 FxxA structure_element Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
31 35 BRC4 chemical Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
60 68 bound to protein_state Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
69 78 truncated protein_state Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
79 84 human species Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
85 90 RAD51 protein Conservation of FxxA motif (A) BRC4 peptide (green cartoon) bound to truncated human RAD51 (grey surface) (PDB: 1n0w, 11). FIG |
|
35 58 FxxA interaction pocket site The blue dashed box highlights the FxxA interaction pocket. FIG |
|
41 46 RAD51 protein (B) Two interacting protein molecules of RAD51 from Saccharomyces cerevisiae are shown. FIG |
|
52 76 Saccharomyces cerevisiae species (B) Two interacting protein molecules of RAD51 from Saccharomyces cerevisiae are shown. FIG |
|
4 9 RAD51 protein One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG |
|
61 66 RAD51 protein One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG |
|
99 110 FxxA pocket site One RAD51 (green cartoon) interacts with another molecule of RAD51 (grey and pink surface) via the FxxA pocket indicated by the dashed blue box. FIG |
|
29 34 RAD51 protein The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
35 43 protomer oligomeric_state The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
130 138 protomer oligomeric_state The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
141 170 FxxA oligomerisation sequence structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
208 212 FxxA structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
230 235 human species The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
236 247 BRC repeats structure_element The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
266 276 eukaryotic taxonomy_domain The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
277 283 RAD51s protein_type The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
291 296 RadAs protein_type The N‐terminal domain of one RAD51 protomer is highlighted in pink for clarity and the green arrow indicates the location of this protomer's FxxA oligomerisation sequence (PDB: 1szp, 29). (C) Conservation of FxxA motif across the human BRC repeats and (D) across 21 eukaryotic RAD51s and 24 RadAs, with the size of the letters proportional to the degree of conservation. FIG |
|
8 29 mutated and truncated experimental_method We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
34 46 tetrapeptide chemical We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
55 59 FHTA structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
115 131 binding affinity evidence We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
137 146 humanised protein_state We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
147 151 RadA protein We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
198 202 FHTA structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
250 260 BRC repeat structure_element We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
262 266 BRC4 chemical We have mutated and truncated the tetrapeptide epitope FHTA, and examined the effects both structurally and on the binding affinity with humanised RadA. As a comparative reference, we are using the FHTA sequence derived from the most tightly binding BRC repeat, BRC4 22. RESULTS |
|
22 34 N‐acetylated protein_state The peptides used are N‐acetylated and C‐amide terminated in order to provide the most relevant peptide in the context of a longer peptide chain. RESULTS |
|
49 52 K D evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS |
|
70 73 ITC experimental_method A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS |
|
97 99 ΔH evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS |
|
104 107 TΔS evidence A summary of the peptide sequence, PDB codes and K D data measured by ITC with the corresponding ΔH and TΔS values are collated in Table 2. RESULTS |
|
0 7 Phe1524 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
11 15 BRC4 chemical Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
33 47 surface pocket site Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
51 56 human species Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
57 62 RAD51 protein Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
115 121 Met158 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
123 129 Ile160 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
131 137 Ala192 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
139 145 Leu203 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
150 156 Met210 residue_name_number Phe1524 of BRC4 binds in a small surface pocket of human RAD51, defined by the hydrophobic side chains of residues Met158, Ile160, Ala192, Leu203 and Met210. RESULTS |
|
15 31 highly conserved protein_state The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS |
|
39 50 BRC repeats structure_element The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS |
|
55 80 oligomerisation sequences structure_element The residue is highly conserved across BRC repeats and oligomerisation sequences. RESULTS |
|
26 35 truncated protein_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
36 39 HTA structure_element Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
40 50 tripeptide chemical Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
84 93 humanised protein_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
95 104 monomeric oligomeric_state Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
105 109 RadA protein Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
111 119 HumRadA2 mutant Consistent with this, the truncated HTA tripeptide could not be detected to bind to humanised, monomeric RadA, HumRadA2 (Table 2, entry 13). RESULTS |
|
53 65 substituting experimental_method As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS |
|
68 78 tryptophan residue_name As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS |
|
87 100 phenylalanine residue_name As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS |
|
150 154 BRC4 chemical As previously discussed, there is some evidence that substituting a tryptophan for the phenylalanine at this position was tolerated in the context of BRC4 12. RESULTS |
|
15 19 WHTA structure_element Therefore, the WHTA peptide was tested and found to not only be tolerated, but to increase the binding affinity of the peptide approximately threefold. RESULTS |
|
95 111 binding affinity evidence Therefore, the WHTA peptide was tested and found to not only be tolerated, but to increase the binding affinity of the peptide approximately threefold. RESULTS |
|
27 39 tetrapeptide chemical The second position of the tetrapeptide was found to be largely invariant to changes in the side chains that were investigated. RESULTS |
|
43 48 RAD51 protein The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS |
|
83 96 hydrogen bond bond_interaction The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS |
|
102 109 Thr1520 residue_name_number The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS |
|
128 132 BRC4 chemical The residue makes no interactions with the RAD51 protein, but may make an internal hydrogen bond with Thr1520 in the context of BRC4, Fig. 3A. RESULTS |
|
0 9 Replacing experimental_method Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS |
|
14 23 histidine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS |
|
32 42 asparagine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS |
|
76 89 hydrogen bond bond_interaction Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS |
|
115 124 histidine residue_name Replacing the histidine with an asparagine, chosen to potentially mimic the hydrogen bond donor–acceptor nature of histidine, resulted in a moderate, twofold decrease in potency (Table 2, entry 4). RESULTS |
|
0 8 Mutating experimental_method Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS |
|
15 22 alanine residue_name Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS |
|
53 57 FHTA structure_element Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS |
|
98 107 histidine residue_name Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS |
|
137 153 binding affinity evidence Mutating to an alanine, recapitulated the potency of FHTA, implying that the interactions made by histidine do not contribute overall to binding affinity (Table 2, entry 3). RESULTS |
|
0 4 FPTA structure_element FPTA was also tested, but was found to have no affinity for the protein (Table 2, entry 5). RESULTS |
|
47 55 affinity evidence FPTA was also tested, but was found to have no affinity for the protein (Table 2, entry 5). RESULTS |
|
26 33 proline residue_name Modelling suggests that a proline in the second position would be expected to clash sterically with the surface of the protein, and provides a rationale for the lack of binding observed. RESULTS |
|
0 9 Threonine residue_name Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS |
|
14 21 mutated experimental_method Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS |
|
28 35 alanine residue_name Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS |
|
75 78 K D evidence Threonine was mutated to an alanine, resulting in only a moderately weaker K D (twofold, Table 2, entry 7). RESULTS |
|
20 32 tetrapeptide chemical In the context of a tetrapeptide at least, this result implies a lack of importance of a threonine at this position. RESULTS |
|
89 98 threonine residue_name In the context of a tetrapeptide at least, this result implies a lack of importance of a threonine at this position. RESULTS |
|
35 42 proline residue_name Interestingly, it was found that a proline at this position improved the affinity almost threefold, to 113 μm (Table 2, entry 6). RESULTS |
|
73 81 affinity evidence Interestingly, it was found that a proline at this position improved the affinity almost threefold, to 113 μm (Table 2, entry 6). RESULTS |
|
16 24 mutation experimental_method This beneficial mutation was incorporated with another previously identified variant to produce the peptide WHPA. RESULTS |
|
108 112 WHPA structure_element This beneficial mutation was incorporated with another previously identified variant to produce the peptide WHPA. RESULTS |
|
28 41 phenylalanine residue_name While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS |
|
93 110 crystal structure evidence While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS |
|
116 123 alanine residue_name While the importance of the phenylalanine may be possible to predict from examination of the crystal structure, the alanine appears to be of much less importance in this regard. RESULTS |
|
18 34 highly conserved protein_state It is, however, a highly conserved residue and clearly of interest for systematic mutation. RESULTS |
|
0 8 Removing experimental_method Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS |
|
13 20 alanine residue_name Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS |
|
51 60 truncated protein_state Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS |
|
61 71 tripeptide chemical Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS |
|
72 75 FHT structure_element Removing the alanine residue entirely produced the truncated tripeptide FHT, which did not bind (Table 2, entry 12). RESULTS |
|
26 46 α‐amino butyric acid chemical The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS |
|
48 49 U chemical The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS |
|
127 141 alanine pocket site The unnatural amino acid, α‐amino butyric acid (U), was introduced at the fourth position, positioning an ethyl group into the alanine pocket (Table 2, entry 9). RESULTS |
|
50 58 affinity evidence Perhaps surprisingly, it was accommodated and the affinity dropped only by twofold as compared to FHTA. RESULTS |
|
98 102 FHTA structure_element Perhaps surprisingly, it was accommodated and the affinity dropped only by twofold as compared to FHTA. RESULTS |
|
21 29 removing experimental_method The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
46 53 alanine residue_name The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
58 69 mutation to experimental_method The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
70 77 glycine residue_name The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
79 83 FHTG structure_element The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
128 144 binding affinity evidence The effect of simply removing the β‐carbon of alanine, by mutation to glycine (FHTG), produced an approximately sixfold drop in binding affinity (Table 2, entry 8). RESULTS |
|
42 49 alanine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
53 71 not 100% conserved protein_state This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
81 88 archeal taxonomy_domain This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
89 102 RadA proteins protein_type This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
113 120 glycine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
137 144 alanine residue_name This is in line with the observation that alanine is not 100% conserved and some archeal RadA proteins contain a glycine in the place of alanine 23. RESULTS |
|
0 27 Structural characterisation experimental_method Structural characterisation of peptide complexes RESULTS |
|
0 10 Structures evidence Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
22 35 tetrapeptides chemical Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
51 63 soaking into experimental_method Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
64 72 crystals evidence Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
78 87 humanised protein_state Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
96 101 RAD51 protein Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
103 111 HumRadA1 mutant Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
184 189 RAD51 protein Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
190 205 crystallography experimental_method Structures of the key tetrapeptides were solved by soaking into crystals of a humanised form of RAD51, HumRadA1, which we have previously reported as a convenient surrogate system for RAD51 crystallography 15. RESULTS |
|
57 78 crystallographic data evidence The corresponding PDB codes are indicated in Table 2 and crystallographic data are found in the Supporting Information. RESULTS |
|
4 14 structures evidence All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS |
|
58 74 electron density evidence All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS |
|
144 154 unliganded protein_state All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS |
|
155 159 RadA protein All structures are of high resolution (1.2–1.7 Å) and the electron density for the peptide was clearly visible after the first refinement using unliganded RadA coordinates (Fig. S1). RESULTS |
|
32 48 binding analysis experimental_method Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS |
|
86 91 X‐ray experimental_method Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS |
|
92 110 crystal structures evidence Some of the SAR observed in the binding analysis can be interpreted in terms of these X‐ray crystal structures. RESULTS |
|
16 23 overlay experimental_method For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
58 62 FHTA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
67 71 FHPA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
191 198 proline residue_name For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
222 226 FHTA structure_element For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
263 279 entropic penalty evidence For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
331 339 affinity evidence For example, an overlay of the bound poses of the ligands FHTA and FHPA (Fig. 2B) reveals a high similarity in the binding modes, indicating that the conformational rigidity conferred by the proline is compatible with the FHTA‐binding mode, and a reduction in an entropic penalty of binding may be the source of the improvement in affinity. RESULTS |
|
0 4 WHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS |
|
59 63 FHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS |
|
109 113 WHTA structure_element WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS |
|
253 263 Phe pocket site WHTA peptide shows a relative dislocation when compared to FHTA (Fig 2A), with the entire ligand backbone of WHTA shifted to accommodate the change in the position of the main chain carbon of the first residue, as the larger indole side chain fills the Phe pocket. RESULTS |
|
44 51 alanine residue_name This shift is translated all the way to the alanine side chain. RESULTS |
|
25 33 mutation experimental_method It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS |
|
55 67 tetrapeptide chemical It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS |
|
95 106 full‐length protein_state It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS |
|
107 111 BRC4 chemical It is possible that this mutation is beneficial in the tetrapeptide context and neutral in the full‐length BRC4 context because the smaller peptide is less constrained and allowed to explore more conformations. RESULTS |
|
31 41 tryptophan residue_name An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS |
|
46 53 proline residue_name An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS |
|
54 63 mutations experimental_method An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS |
|
100 104 WHPA structure_element An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS |
|
125 129 FHTA structure_element An attempt to combine both the tryptophan and proline mutations, however, led to no improvement for WHPA peptide compared to FHTA. RESULTS |
|
72 76 WHTA structure_element One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS |
|
141 148 proline residue_name One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS |
|
152 156 WHPA structure_element One possible explanation is that the ‘shifted’ binding mode observed in WHTA was not compatible with the conformational restriction that the proline of WHPA introduced. RESULTS |
|
46 53 Overlay experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
59 63 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
75 79 WHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
156 169 Superposition experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
173 177 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
189 193 FHPA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
253 260 Overlay experimental_method Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
264 268 FHTU structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
278 282 FHTA structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
294 298 FHTG structure_element Comparison of different peptide complexes (A) Overlay with FHTA (grey) and WHTA (purple) showing a small relative displacement of the peptide backbone. (B) Superposition of FHTA (grey) and FHPA (yellow), showing conservation of backbone orientation (C) Overlay of FHTU (green), FHTA (grey) and FHTG (cyan). FIG |
|
4 22 thermodynamic data evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
91 109 thermodynamic data evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
127 132 X‐ray experimental_method The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
133 155 structural information evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
172 178 mutant protein_state The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
179 187 peptides chemical The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
235 257 thermodynamic profiles evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
295 298 ΔΔH evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
303 306 ΔΔS evidence The thermodynamic data of peptide binding are also shown in Table 2. Although we have both thermodynamic data and high‐quality X‐ray structural information for some of the mutant peptides, we do not attempt to interpret differences in thermodynamic profiles between ligands, that is, to analyse ΔΔH and ΔΔS. RESULTS |
|
9 11 ΔH evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS |
|
16 18 ΔS evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS |
|
38 42 K Ds evidence Although ΔH and ΔS are tabulated, the K Ds measured are relatively weak and necessarily performed under low c‐value conditions. RESULTS |
|
87 89 ΔH evidence In this experimental regime, nonsigmoidal curves are generated and therefore errors in ΔH are expected to be much higher than the errors from model fitting given in Table 2 16. RESULTS |
|
3 5 ΔS evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS |
|
22 24 ΔG evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS |
|
40 42 ΔH evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS |
|
54 56 ΔH evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS |
|
91 93 ΔS evidence As ΔS is derived from ΔG by subtracting ΔH, errors in ΔH will be correlated with errors in ΔS, giving rise to a ‘phantom’ enthalpy–entropy compensation. RESULTS |
|
125 128 ΔΔH evidence Such effects have been discussed by Klebe 24 and Chodera and Mobley 25 and will frustrate attempts to interpret the measured ΔΔH and ΔΔS. RESULTS |
|
133 136 ΔΔS evidence Such effects have been discussed by Klebe 24 and Chodera and Mobley 25 and will frustrate attempts to interpret the measured ΔΔH and ΔΔS. RESULTS |
|
4 13 conserved protein_state The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS |
|
14 27 phenylalanine residue_name The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS |
|
32 39 alanine residue_name The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS |
|
56 60 FHTA structure_element The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS |
|
117 120 ITC experimental_method The conserved phenylalanine and alanine residues of the FHTA sequence were both found to be essential for binding by ITC. RESULTS |
|
31 40 histidine residue_name Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
71 82 unconserved protein_state Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
83 90 His1525 residue_name_number Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
98 102 BRC4 chemical Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
122 129 mutated experimental_method Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
164 180 peptide affinity evidence Conversely the second position histidine residue, corresponding to the unconserved His1525 in the BRC4 sequence, could be mutated without significant effect on the peptide affinity. RESULTS |
|
37 45 hot‐spot site The more general correlation between hot‐spot residues in protein–protein interactions and the high conservation of such residues has been previously reported 10, 26. RESULTS |
|
95 112 high conservation protein_state The more general correlation between hot‐spot residues in protein–protein interactions and the high conservation of such residues has been previously reported 10, 26. RESULTS |
|
28 44 highly conserved protein_state Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS |
|
45 54 threonine residue_name Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS |
|
72 79 mutated experimental_method Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS |
|
102 118 peptide affinity evidence Interestingly, however, the highly conserved threonine residue could be mutated without affecting the peptide affinity. RESULTS |
|
49 66 high conservation protein_state This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS |
|
74 77 BRC structure_element This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS |
|
82 107 oligomerisation sequences structure_element This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS |
|
147 154 Thr1526 residue_name_number This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS |
|
244 268 alanine mutation studies experimental_method This unexpected result, in the light of its very high conservation in the BRC and oligomerisation sequences, begs the question of what the role of Thr1526 is and highlights a potential pitfall and need for caution in the experimental design of alanine mutation studies. RESULTS |
|
7 11 FHTA structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
12 19 peptide chemical As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
68 78 BRC repeat structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
96 101 RAD51 protein As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
102 130 self‐oligomerisation peptide structure_element As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
168 175 Thr1526 residue_name_number As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
177 181 BRC4 chemical As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
201 206 Thr87 residue_name_number As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
208 213 RAD51 protein As the FHTA peptide is potentially a surrogate peptide for both the BRC repeat peptides and the RAD51 self‐oligomerisation peptide, it is useful to examine the role of Thr1526 (BRC4) and the analogous Thr87 (RAD51) in both binding contexts in more detail. RESULTS |
|
9 18 structure evidence Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS |
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22 26 BRC4 chemical Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS |
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40 55 in complex with protein_state Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS |
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56 61 human species Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS |
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62 67 RAD51 protein Only one structure of BRC4 is published in complex with human RAD51 (PDB: 1n0w). RESULTS |
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36 40 BRC4 chemical Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS |
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46 54 bound to protein_state Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS |
|
55 60 RAD51 protein Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS |
|
82 96 hydrogen bonds bond_interaction Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS |
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114 118 BRC4 chemical Figure 3A shows the binding pose of BRC4 when bound to RAD51 and the intrapeptide hydrogen bonds that are made by BRC4. RESULTS |
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6 13 Phe1524 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
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18 25 Ala1527 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
40 59 hydrophobic pockets site While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
76 83 His1525 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
110 123 hydrogen bond bond_interaction While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
145 152 Thr1520 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
173 180 His1525 residue_name_number While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
214 219 water chemical While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
254 270 hydrogen bonding bond_interaction While Phe1524 and Ala1527 are buried in hydrophobic pockets on the surface, His1525 is close enough to form a hydrogen bond with the carbonyl of Thr1520, but the rotamer of His1525, supported by clearly positioned water molecules, is not compatible with hydrogen bonding. RESULTS |
|
6 13 Thr1520 residue_name_number Also, Thr1520 is constrained by crystal contacts in this structure. RESULTS |
|
57 66 structure evidence Also, Thr1520 is constrained by crystal contacts in this structure. RESULTS |
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0 20 Lack of conservation protein_state Lack of conservation of this residue supports the idea that this interaction is not crucial for RAD51:BRC repeat binding. RESULTS |
|
96 112 RAD51:BRC repeat complex_assembly Lack of conservation of this residue supports the idea that this interaction is not crucial for RAD51:BRC repeat binding. RESULTS |
|
23 27 BRC4 chemical (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
46 54 bound to protein_state (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
55 60 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
166 189 oligomerisation epitope structure_element (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
193 206 S. cerevisiae species (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
208 213 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
219 227 bound to protein_state (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
233 238 RAD51 protein (A) Highlight of intra‐BRC4 interactions when bound to RAD51 (omitted for clarity) (PDB: 1n0w), with key residues shown in colour. (B) Intrapeptide interactions from oligomerisation epitope of S. cerevisiae RAD51 when bound to next RAD51 in the filament (PDB: 1szp). FIG |
|
33 46 S. cerevisiae species Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG |
|
48 53 RAD51 protein Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG |
|
81 86 human species Residue numbering relates to the S. cerevisiae RAD51 protein, the corresponding human residues are in parentheses. FIG |
|
9 18 threonine residue_name Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS |
|
22 28 serine residue_name Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS |
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81 85 FxxA structure_element Either a threonine or serine is most commonly found in the third position of the FxxA motif. RESULTS |
|
0 7 Thr1526 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
46 51 RAD51 protein Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
81 102 hydrogen bond network bond_interaction Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
112 128 highly conserved protein_state Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
129 134 S1528 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
139 144 K1530 residue_name_number Thr1526 makes no direct interactions with the RAD51 protein, but instead forms a hydrogen bond network with the highly conserved S1528 and K1530 (Fig. 1C). RESULTS |
|
4 31 high degree of conservation protein_state The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS |
|
199 215 interaction site site The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS |
|
231 236 RAD51 protein The high degree of conservation of these three residues suggests an important possible role in facilitating a turn and stabilising the conformation of the peptide as it continues its way to a second interaction site on the side of RAD51. RESULTS |
|
34 45 RAD51:RAD51 complex_assembly With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
62 67 human species With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
68 85 crystal structure evidence With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
134 144 structures evidence With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
148 156 archaeal taxonomy_domain With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
157 161 RadA protein With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
178 202 Saccharomyces cerevisiae species With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
203 208 RAD51 protein With respect to understanding the RAD51:RAD51 interaction, no human crystal structure has been published, however, several oligomeric structures of archaeal RadA as well that of Saccharomyces cerevisiae RAD51 have been reported 27, 28, 29. RESULTS |
|
35 39 FxxA structure_element Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
51 74 oligomerisation peptide structure_element Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
84 97 S. cerevisiae species Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
98 103 RAD51 protein Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
104 113 structure evidence Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
165 170 human species Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
171 176 RAD51 protein Figure 3B shows a highlight of the FxxA portion of oligomerisation peptide from the S. cerevisiae RAD51 structure, with residues in parentheses corresponding to the human RAD51 protein. RESULTS |
|
4 13 conserved protein_state The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS |
|
14 23 threonine residue_name The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS |
|
62 75 hydrogen bond bond_interaction The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS |
|
136 143 α‐helix structure_element The conserved threonine residue at the third position forms a hydrogen bond with the peptide backbone amide, which forms the base of an α‐helix. RESULTS |
|
60 69 threonine residue_name In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
73 77 FxxA structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
128 134 β‐turn structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
150 153 BRC structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
169 176 α‐helix structure_element In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
192 197 RAD51 protein In both structural contexts, the role of the third position threonine in FxxA seems to be in stabilising secondary structure |
|
7 19 tetrapeptide chemical In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS |
|
77 85 mutation experimental_method In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS |
|
89 98 threonine residue_name In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS |
|
102 109 alanine residue_name In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS |
|
153 161 affinity evidence In the tetrapeptide context these secondary interactions are not present and mutation of threonine to alanine would be expected to have little effect on affinity. RESULTS |
|
69 85 peptide affinity evidence In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS |
|
280 284 BRC4 chemical In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS |
|
302 325 oligomerisation peptide structure_element In line with this, although we observe a slight twofold weakening of peptide affinity, the effect is far from being as drastic or inactivating as reported in longer peptide backgrounds 3. It would be interesting to investigate the importance of this residue in the context of the BRC4 peptide, and the oligomerisation peptide. RESULTS |
|
28 35 alanine residue_name Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS |
|
36 44 mutation experimental_method Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS |
|
167 171 BRC3 chemical Rather than indifference to alanine mutation, a significant effect, via lack of secondary structure stabilisation, would be predicted, as indeed has been reported for BRC3 3. RESULTS |
|
20 24 FxxA structure_element Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL |
|
32 45 phenylalanine residue_name Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL |
|
50 57 alanine residue_name Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL |
|
63 79 highly conserved protein_state Two residues in the FxxA motif, phenylalanine and alanine, are highly conserved (Fig 4a). CONCL |
|
0 13 Phenylalanine residue_name Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL |
|
14 24 mutated to experimental_method Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL |
|
25 35 tryptophan residue_name Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL |
|
59 71 tetrapeptide chemical Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL |
|
163 167 BRC4 chemical Phenylalanine mutated to tryptophan, in the context of the tetrapeptide improved potency, contrary to the reported result of comparable activity in the context of BRC4 12. CONCL |
|
0 7 Proline residue_name Proline at the third position similarly improved potency. CONCL |
|
21 29 mutating experimental_method Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL |
|
43 50 alanine residue_name Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL |
|
54 61 glycine residue_name Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL |
|
101 121 α‐amino butyric acid chemical Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL |
|
123 124 U chemical Activity was lost by mutating the terminal alanine to glycine, but recovered somewhat with the novel α‐amino butyric acid (U). CONCL |
|
0 9 Threonine residue_name Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL |
|
56 69 tetrapeptides chemical Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL |
|
135 139 BRC3 chemical Threonine was found to be relatively unimportant in the tetrapeptides but has been previously reported to be crucial in the context of BRC3. CONCL |
|
58 67 threonine residue_name The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL |
|
100 106 β‐turn structure_element The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL |
|
114 125 BRC repeats structure_element The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL |
|
150 163 tetrapeptides chemical The reason for this disconnection is suggested to be that threonine plays a role in stabilising the β‐turn in the BRC repeats, which is absent in the tetrapeptides studied. CONCL |
|
46 54 hot‐spot site This may lead to a more general caution, that hot‐spot data should be interpreted by considering the bound interaction with the protein, as well as the potential role in stabilising the bound peptide secondary structure. CONCL |
|
78 106 alanine‐scanning experiments experimental_method In either case, the requirement for structural data in correctly interpreting alanine‐scanning experiments is reinforced. CONCL |
|
32 36 FxxA structure_element Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG |
|
68 73 Rad51 protein Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG |
|
104 115 BRC repeats structure_element Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG |
|
157 169 tetrapeptide chemical Summary of key observations (A) FxxA motif sequence conservation of Rad51 oligomerisation sequences and BRC repeats. (B) Highlight of SAR identified for the tetrapeptide. FIG |
|
19 21 ΔG evidence The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
65 69 FHTA structure_element The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
130 148 structural overlay experimental_method The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
160 167 Overlay experimental_method The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
171 183 tetrapeptide chemical The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
184 194 structures evidence The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
201 210 wild‐type protein_state The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
211 215 FHTA structure_element The differences in ΔG for different peptide variants relative to FHTA are shown in the bar chart with colouring matching with the structural overlay below. (C) Overlay of tetrapeptide structures, with wild‐type FHTA peptide across the figure for reference and truncated segments of mutated residues shown in each panel. FIG |
|
17 21 WHTA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG |
|
37 41 FATA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG |
|
53 57 FHPA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG |
|
67 71 FHTG structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG |
|
91 95 FHTA structure_element Purple carbon is WHTA, light blue is FATA, yellow is FHPA, cyan is FHTG and grey carbon is FHTA. FIG |
|
46 50 FHTG structure_element Note the C‐terminal amide changes position in FHTG without the anchoring methyl group. FIG |
|
|
