LiteFold/DisProt huggingface dataset:
Protein: DP00021 (UniProt P13551)
Region: residues 44	to 63
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The PDB shows this region lacks electron density, indicating it is disordered.
Cross-references: PDB:2BM0
Protein: DP00021 (UniProt P13551)
Region: residues 42	to 60
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Switch I is invisible between residues 43 and 60, and residues 40–41 and 61–65 can only be built as poly-alanine.
The PDB shows the IDR boundaries are 42-60.
Cross-references: PDB:2BV3
Protein: DP00021 (UniProt P13551)
Region: residues 40	to 67
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Switch I (the effector loop) is a highly flexible region in all G-proteins.
Cross-references: PDB:1FNM
Protein: DP00021 (UniProt P13551)
Region: residues 416	to 434
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The PDB shows this region lacks electron density, indicating it is disordered.
Cross-references: PDB:2BV3
Protein: DP00021 (UniProt P13551)
Region: residues 464	to 475
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The PDB shows this region lacks electron density, indicating it is disordered.
Cross-references: PDB:2BV3
Protein: DP00023 (UniProt P14061)
Region: residues 286	to 328
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
However, the α-carbon chain cannot be traced beyond residue 284 because the electron density is so diffuse.
Interestingly, the electron density for the C terminus, which is rich in alanine, glycine, proline and other hydrophobic residues, is ill defined beyond the end of αH at position 285. 
Cross-references: PDB:1BHS
Protein: DP00023 (UniProt P14061)
Region: residues 191	to 199
Annotation: flexible linker (Disorder function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
These structures provide a complete picture of the NADP+-enzyme interactions involving the flexible 191–199 loop (well ordered in the H221L mutant) and suggest that the hydrophobic residues Phe192-Met193 could facilitate hydride transfer.
In the H221L-NAD1 complex, where a sulfate ion replaces the 2'-phosphate, the electron density corresponding to the 191–199 loop is less well defined even though the NAD1 site appears to be fully occupied. This implies that although the sulfate ion establishes a series of interactions with both the protein and the cofactor, these are less efficient in stabilizing the 191–199 loop than those formed by the covalently bound 2'-phosphate.
 This loop, which becomes well ordered only in the enzyme-
NADP+-folate complex, has been found to shield the nicotinamide moiety from solvent and to participate on the transition state stabilization (44).
The 191–199 loop, located between the bF sheet and the aG helix, seems to be predominantly stabilized by its interactions with the dinucleotide, particularly by the salt bridge between Lys195 and the 2'-phosphate.
Cross-references: PDB:1FDU
PDB:1FDV
Protein: DP00023 (UniProt P14061)
Region: residues 191	to 199
Annotation: small molecule binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
In the H221L-NAD1 complex, where a sulfate ion replaces the 2'-phosphate, the electron density corresponding to the 191–199 loop is less well defined even though the NAD1 site appears to be fully occupied. This implies that although the sulfate ion establishes a series of interactions with both the protein and the cofactor, these are less efficient in stabilizing the 191–199 loop than those formed by the covalently bound 2'-phosphate.
The 191–199 loop, located between the bF sheet and the aG helix, seems to be predominantly stabilized by its interactions with the dinucleotide, particularly by the salt bridge between Lys195 and the 2'-phosphate.
Cross-references: PDB:1FDU
PDB:1FDV
Protein: DP00023 (UniProt P14061)
Region: residues 286	to 328
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The C-terminal region is missing in the pdb structures.
Cross-references: PDB:1FDU
PDB:1FDV
PDB:1FDW
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
When exposed to an acidic environment, E7(1-40) undergoes a structural transition triggered by the
neutralization of its acidic residues, similar to the full-length HPV16 E7 dimer (7). A decrease in the CD signal at 220 nm at low pH is indicative of the acquisition of R-helix. Moreover, as pH decreases, the CD indicates that the PII content tends to disappear.
The N-terminus could thus be responsible for E7's conformational behavior toward pH; it undergoes a conformational transition within a physiological pH range that could correspond to an induction in α-helix and/or loss of PII structure. The difference spectrum between E7(1−40) at pH 7.5 and pH 3.0 displays the positive distinctive band at 218 nm present in PII models (Figure 2b inset).
This result is in excellent agreement with the observed conformational transition by CD, where the molar ellipticity at 220 nm decreased when the pH is lowered (not shown).
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The far-UV CD spectrum of the E7 dimer (E72) at pH 7.5 is dominated by a minimum at 205 nm, with a negative band at around 220 nm (Figure 2a, dotted line). The band at 220 nm is indicative of α-helix content, and the minimum at 205 can be the result of a combination of an α-helix (208 nm) and disordered structure (200 nm). When observing the spectrum of the N-terminus of E7, it is reminiscent of that of a disordered polypeptide with a minimum around 200 nm (Figure 2a, full line). To analyze the structural contribution of the E7(1−40) domain to the E72 far-UV−CD, the subtraction of spectra was carried out and presents only the α-helix spectral characteristics, suggesting that the apparently disordered components in the E7 dimer, manifested by the minimum at 205 nm, are introduced by the N-terminal module (Figure 2a, inset), in agreement with the solved structure of HPV 1A E7 where the N-terminal region is absent in the crystal ( 5) and HPV 45 E7 N-terminus not analyzable by NMR ( 4).
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: gel-filtration evidence used in manual assertion
Supporting statements:
At pH 7.5, E7(1−40) elutes at 15 mL, while CI2(1−40) does so at 17 mL, indicating that at neutral pH, E7(1−40) is extended (Figure 3). E7(1−40) elutes with the hydrodynamic volume of a globular protein of 25 kDa, equivalent to a Stokes radius of 20.9 Å, a value even larger than the predicted for a “natively unfolded” polypeptide of this size.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In addition, we carried out pulse field gradient NMR experiments at 1 mM E7(1−40), and from the diffusion coefficient the domain was shown to be monomeric, with a calculated stokes radius of 21.26 Å, expected for an extended fragment of that number of residues (not shown).
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In addition, we carried out pulse field gradient NMR experiments at 1 mM E7(1−40), and from the diffusion coefficient the domain was shown to be monomeric, with a calculated stokes radius of 21.26 Å, expected for an extended fragment of that number of residues (not shown). When the same experiment is carried out at pH 4.0, the hydrodynamic volume of CI2(1−40) stays unmodified, but E7(1−40) elutes at a larger volume from the column, strongly suggesting that the conformational change induced at low pH yields a more compact structure (Figure 3).
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Comparison of the far-UV CD spectra of the E7N sub-fragments in 10 mM Tris.Cl buffer at pH 7.5 showed a lack of canonical secondary structure with a general appearance of disorder (Figure 2A). Most sub-fragments presented similar spectra, with molar ellipticity values around −15,000 deg·cm2·dmol−1 resembling those of the previously described E7 (1–40) domain [27].
They assessed the regions: 1-40, 1-20, 16-40, 16-31, 21-29 and 25-40. For all of them they found typical spectra of unstructured proteins.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Both RH values obtained for E7N were significantly larger than the RH value expected for a 40 residue globular protein (13.8 Å) [51], confirming the IDP nature of E7N. However, both values were also smaller than the RH value predicted for a fully unfolded polymer (18.1 Å) [51], which suggested some degree of compaction of the domain that may be due to the presence of transient long-range interactions. PFG-NMR experiments showed a further decrease in the RH value at pH 5.0 (14.3±0.3 Å, Table 3), suggesting that protonation of the acidic residues contributed to E7N compaction.
 A first inspection of the one dimensional 1H spectrum of E7N in aqueous solution at pH 5.0 showed poorly dispersed amide proton resonances (data not shown), with most peaks within the 7.8–8.5 ppm range, making assignment a rather challenging task. The methyl proton region also showed poor dispersion of peaks, confirming the expected disordered nature of E7N.
Cross-references: BMRB:19269
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 46
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
All the NMR data determined for the E7N region indicate that it is highly flexible and highly disordered, as is also immediately evident from the SSP values as well as from negative 1H–15N heteronuclear NOE. Detailed inspection of these data also indicates short fragments of amino acids characterized by a mild secondary structural propensity, starting at residue 26 onwards (Figure 4).
Cross-references: BMRB:19442
Protein: DP00024 (UniProt P03129)
Region: residues 21	to 29
Annotation: viral process (Biological process)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Crystal structures of the p107 pocket domain in complex with LIN5212–34;phosS28 and E721–29. (Insets, left) The LIN52 and E7 peptides both bind at the LxCxE cleft. (Inset, top) The LIN52 association is mediated by the S28 phosphate, which contacts a p107/p130-specific binding pocket.
The E7 peptide binds to the LxCxE cleft in the B-box of p107 as previously observed in the Rb–E7 complex structure (Fig. 2; Supplemental Fig. 2B; Lee et al. 1998).
Cross-references: PDB:4YOZ
Protein: DP00024 (UniProt P03129)
Region: residues 21	to 29
Annotation: protein binding (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
Crystal structures of the p107 pocket domain in complex with LIN5212–34;phosS28 and E721–29. (Insets, left) The LIN52 and E7 peptides both bind at the LxCxE cleft. (Inset, top) The LIN52 association is mediated by the S28 phosphate, which contacts a p107/p130-specific binding pocket.
The E7 peptide binds to the LxCxE cleft in the B-box of p107 as previously observed in the Rb–E7 complex structure (Fig. 2; Supplemental Fig. 2B; Lee et al. 1998).
Cross-references: PDB:4YOZ
Protein: DP00024 (UniProt P03129)
Region: residues 21	to 29
Annotation: protein binding (Molecular function)
Evidence: fluorescence polarization evidence used in manual assertion
Supporting statements:
We then quantified the E7 peptide inhibition (Ki = 170 ± 50 nM) by displacing labeled LIN5212–34;phosS28 peptide in the FP assay (Fig. 1F). E721–29 contains an LxCxExL motif and inhibits LIN52 from interacting with p130, indicating that E7 disrupts DREAM by competitive inhibition at the LxCxE cleft of p130.
Protein: DP00024 (UniProt P03129)
Region: residues 16	to 40
Annotation: protein binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
This implies that there is one binding site for the E7(1-40) peptide per RbAB monomer and that the stoichiometry of the E7(1-40)–RbAB interaction is 1 : 1.
The CR1 region does not appear to contribute to RbAB binding within the context of an E7N monomer, as shown by the fact that the E7(16-40) and E7(1-40) peptides have the same affinity for the RbAB domain (Table 1).
Therefore, our data show that the LxCxE motif contributes about 90% of the total binding energy for the HPV16 E7–RbAB interaction, providing quantitative support to previous results [[47]].
Protein: DP00024 (UniProt P03129)
Region: residues 16	to 40
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
We tested the E7 CR2 region for PII content by measuring the far-UV CD spectra of the E7(16-40) and the E7(16-40)PP peptides at 5 °C. Both peptides presented a CD spectrum characteristic for a disordered polypeptide with a positive band at 218 nm, which is characteristic of the PII conformation (Fig. 5A).
Overall, our data indicate that both peptides from the HPV16 E7 CR2 region present residual PII structure in equilibrium with disordered conformations.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Far-UV CD analyses showed that HPV16 E7(1-40) displayed an extended PII structure, which was stabilized by phosphorylation of serine residues S31 and S32 [[23]].
Both peptides presented a CD spectrum characteristic for a disordered polypeptide with a positive band at 218 nm, which is characteristic of the PII conformation (Fig. 5A).
Overall, our data indicate that both peptides from the HPV16 E7 CR2 region present residual PII structure in equilibrium with disordered conformations.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: order (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In addition, we carried out pulse field gradient NMR experiments at 1 mM E7(1−40), and from the diffusion coefficient the domain was shown to be monomeric, with a calculated stokes radius of 21.26 Å, expected for an extended fragment of that number of residues (not shown). When the same experiment is carried out at pH 4.0, the hydrodynamic volume of CI2(1-40) stays unmodified, but E7(1-40) elutes at a larger volume from the column, strongly suggesting that the conformational change induced at low pH yields a more compact structure (Figure 3).
At pH 4.0 and below, the negatively charged residues are neutralized, the charge repulsion decreases, and more R-helix is formed.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 40
Annotation: order (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The difference spectrum between E7(1-40) at pH 7.5 and pH 3.0 displays the positive distinctive band at 218 nm present in PII models (Figure 2b inset).
This result is in excellent agreement with the observed conformational transition by CD, where the molar ellipticity at 220 nm decreased when the pH is lowered (not
shown).
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 51
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Using a variety of spectroscopic and biochemical tools, we find that despite its nanomolar affinity, the HPV16 E7 complex with TAZ2 is disordered and highly dynamic. The disordered domain of HPV16 E7 protein does not adopt a single conformation on the surface of TAZ2 but engages promiscuously with its target through multiple interactions involving two conserved motifs, termed CR1 and CR2, that occupy an extensive binding surface on TAZ2.
It is clear from all of the results shown in Figures 2, 3, 6, and 9 that no single E7 structure will be able to satisfy all of the NOE constraints.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 51
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Using a variety of spectroscopic and biochemical tools, we find that despite its nanomolar affinity, the HPV16 E7 complex with TAZ2 is disordered and highly dynamic. The disordered domain of HPV16 E7 protein does not adopt a single conformation on the surface of TAZ2 but engages promiscuously with its target through multiple interactions involving two conserved motifs, termed CR1 and CR2, that occupy an extensive binding surface on TAZ2.
1H-15N HSQC spectra of 15N-labeled ppE7(1−51) titrated with unlabeled TAZ2 show stepwise chemical shift perturbations as a function of increasing molar amounts of TAZ2 (Figure 2A), an indication that the complex and its components are in fast exchange on the NMR chemical shift timescale.
Protein: DP00024 (UniProt P03129)
Region: residues 1	to 51
Annotation: protein binding (Molecular function)
Evidence: fluorescence anisotropy evidence used in manual assertion
Supporting statements:
The anisotropy change was fitted to competition models,55 which provided affinity estimates for the individual competing peptides (Figure 5). The results clearly demonstrate that cooperativity between the CR1 and CR2 binding motifs enhances E7 affinity toward TAZ2.
Only when CR1 and CR2 are both present in the peptide is E7 able to reach its characteristic nM binding affinity (KD 22 nM,37 compared to 100 nM under the current conditions).
Protein: DP00025 (UniProt P14738)
Region: residues 746	to 858
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The far-UV CD spectra of rFNBD-A, rFNBD-B, rFNBD-D, and rFNBD-P were very similar and were dominated by a large minimum at ∼200 nm (Fig. 2). This type of spectra is characteristic of proteins that are predominately composed of random coil and γ-turns and contain a minimum amount of α-helix or β-sheet conformation(15., 16.).
Protein: DP00025 (UniProt P14738)
Region: residues 746	to 858
Annotation: disorder to order (Structural transition)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Because of the defined, stable, secondary and tertiary structure in N29, the minute change in the intrinsic Trp fluorescence in N29 on binding of rFNBD-A, and the apparent lack of stable ordered conformation in the rFNBD proteins, the large conformational shift seen in the far-UV CD on recombinant adhesin binding to N29 is largely attributed to the rFNBD proteins assuming a predominately β-sheet structure on binding to N29.
N29 peptide corresponds to the NH2-terminal domain of the human fibronectin.
Protein: DP00025 (UniProt P14738)
Region: residues 746	to 858
Annotation: protein binding (Molecular function)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Because of the defined, stable, secondary and tertiary structure in N29, the minute change in the intrinsic Trp fluorescence in N29 on binding of rFNBD-A, and the apparent lack of stable ordered conformation in the rFNBD proteins, the large conformational shift seen in the far-UV CD on recombinant adhesin binding to N29 is largely attributed to the rFNBD proteins assuming a predominately β-sheet structure on binding to N29.
N29 peptide corresponds to the NH2-terminal domain of the human fibronectin.
Protein: DP00025 (UniProt P14738)
Region: residues 745	to 874
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the spectra of D1−D4 there is a large amount of resonance overlap, the limited 1H chemical shift dispersion reflecting the unfolded nature of the protein; this severely hampered the sequential assignment process.
Protein: DP00025 (UniProt P14738)
Region: residues 745	to 874
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The unfolded nature of D1-D4 gives rise to very high resolution spectra enabling accurate measurement of NMR parameters. The residue-specific NMR data for D1-D4, including chemical shifts, coupling constants and NOEs, reflect the absence of secondary structure and the predominantly unfolded nature of this protein.
Protein: DP00025 (UniProt P14738)
Region: residues 745	to 874
Annotation: disorder (Structural state)
Evidence: protein thermal shift assay evidence used in manual assertion
Supporting statements:
By monitoring the elution volume (Ve) of rFNBD-B using gel-permeation chromatography as the concentration of GdnHCl was increased from 0 to 6 M, it was determined that rFNBD-B does not follow a cooperative unfolding model (Fig. 3).
Protein: DP00025 (UniProt P14738)
Region: residues 745	to 874
Annotation: disorder (Structural state)
Evidence: fluorescence evidence used in manual assertion
Supporting statements:
It was determined that ANS did not bind to rFNBD-A or rFNBD-B under any conditions tested, indicating that the proteins do not appear to be capable of forming localized, stable regions of hydrophobic side chains (data not shown).
Protein: DP00026 (UniProt P06179)
Region: residues 1	to 65
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
It was found that both termini of flagellin are rapidly degraded in the early steps of proteolysis.
This suggests that there are no significant intrinsic structural constraints in the terminal parts to limit the accessibility of the peptide bonds, i.e. these regions have an exceptionally flexible conformation. The readily hydrolysed terminal portions probably do not have any compact tertiary structure and are in extensive contact with the surrounding media. In contrast, the central region of the molecule, which involves the F40 and F27 fragments is quite stable against proteolysis, indicating that it is probably composed of compact structural units.