LiteFold/DisProt huggingface dataset:
Protein: DP01876 (UniProt P52926)
Region: residues 1	to 109
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Far-UV CD spectropolarimetry of HMGA2 produced a spectrum with a minimum at 199 nm followed by a flat line from 210 to 250 nm. This spectrum appeared identical to that of a disordered protein.
Protein: DP01876 (UniProt P52926)
Region: residues 1	to 109
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The HSQC spectrum of HMGA2 displayed a very narrow chemical shift range in the proton dimension that is highly characteristic of a disordered protein. In particular, the 1H resonances fall between 7.9 and 8.6 ppm.
Protein: DP01876 (UniProt P52926)
Region: residues 1	to 109
Annotation: nucleic acid binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Upon interaction with a replication fork (RF), HMGA2 forms an equimolar complex by binding in a side-by-side orientation. It is necessary for HMGA2 to be in a disordered state such that it has the flexibility to stabilize a stalled RF by binding to the necessary AT-rich sites.
Protein: DP01876 (UniProt P52926)
Region: residues 1	to 109
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
In general, the Kratky analysis of SAXS data for proteins provided qualitative information on the overall shape of the biomolecule of interest. The ascending linear curve (coral) observed for HMGA2 in the Porod-Debye Plateau region was indicative of a disordered protein, which agrees with results from the CD and NMR analyses.
Protein: DP01877 (UniProt Q96AY2)
Region: residues 445	to 455
Annotation: disorder to order (Structural transition)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The disordered loop (residues 445–455) becomes ordered and extends the five-turn helix (a7) to a continuous and kinked (at Pro447) eight-turn helix (Fig 2A–D).
Protein: DP01877 (UniProt Q96AY2)
Region: residues 369	to 402
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The limited proteolytic digestion analysis suggested that residues between 368 and 403 in hEme1 are connected by a highly flexible linker, which we presumed to be a loop region
Cross-references: PDB:2ZIW
PDB:2ZIV
PDB:2ZIU
PDB:2ZIX
Protein: DP01877 (UniProt Q96AY2)
Region: residues 369	to 402
Annotation: DNA binding (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The limited proteolytic digestion analysis suggested that residues between 368 and 403 in hEme1 are connected by a highly flexible linker, which we presumed to be a loop region
Cleavage of the 36R linker of hEme1 into two parts also significantly decreased the nuclease activity and the DNA-binding affinity of the hMUS81ΔN complex. Reducing the size of this cleaved linker of hEme1 by 10 or 26 residues abrogated the DNA-binding and nuclease activities of hMUS81ΔN on 3′ flap and nHJ substrates, demonstrating the importance of this 36R linker in DNA binding and cleavage.
Cross-references: PDB:2ZIW
PDB:2ZIV
PDB:2ZIU
PDB:2ZIX
Protein: DP01877 (UniProt Q96AY2)
Region: residues 369	to 402
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The limited proteolytic digestion analysis suggested that residues between 368 and 403 in hEme1 are connected by a highly flexible linker, which we presumed to be a loop region
Cleavage of the 36R linker of hEme1 into two parts also significantly decreased the nuclease activity and the DNA-binding affinity of the hMUS81ΔN complex. Reducing the size of this cleaved linker of hEme1 by 10 or 26 residues abrogated the DNA-binding and nuclease activities of hMUS81ΔN on 3′ flap and nHJ substrates, demonstrating the importance of this 36R linker in DNA binding and cleavage.
Taken together, we propose that the primary role of the 36R linker is to recognize the duplex portion of a substrate DNA and to stabilize the interaction between the MUS81ΔN complex and the substrate DNA, which appears to be required for efficient cleavage.
Cross-references: PDB:2ZIW
PDB:2ZIV
PDB:2ZIU
PDB:2ZIX
Protein: DP01877 (UniProt Q96AY2)
Region: residues 369	to 402
Annotation: molecular function regulator (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The limited proteolytic digestion analysis suggested that residues between 368 and 403 in hEme1 are connected by a highly flexible linker, which we presumed to be a loop region
Cleavage of the 36R linker of hEme1 into two parts also significantly decreased the nuclease activity and the DNA-binding affinity of the hMUS81ΔN complex. Reducing the size of this cleaved linker of hEme1 by 10 or 26 residues abrogated the DNA-binding and nuclease activities of hMUS81ΔN on 3′ flap and nHJ substrates, demonstrating the importance of this 36R linker in DNA binding and cleavage.
Taken together, we propose that the primary role of the 36R linker is to recognize the duplex portion of a substrate DNA and to stabilize the interaction between the MUS81ΔN complex and the substrate DNA, which appears to be required for efficient cleavage.
Cross-references: PDB:2ZIW
PDB:2ZIV
PDB:2ZIU
PDB:2ZIX
Protein: DP01878 (UniProt Q9UPR3)
Region: residues 924	to 946
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The relatively high Rfree is likely due to the significant proportion of poorly disordered residues
Cross-references: PDB:2HWY
Protein: DP01879 (UniProt Q9JIH2)
Region: residues 47	to 109
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 47–109 of Nup50 were not visible and were probably disordered in the crystal, possibly because this region of Nup50 is rich in glycine.
Cross-references: PDB:2C1M
Protein: DP01880 (UniProt Q15596)
Region: residues 624	to 829
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
2D [1 H,15N]-HSQC NMR analysis of SRC-2 RID (res. 624-829), which contains three LXXLL motifs revealed very poor spectral dispersion and missing peaks which often make the analysis of disordered proteins such as SRC-2 RID problematic. Using 2D and 3D 13C-detected NMR methods, we obtained backbone chemical shift assignments for 213 of the 235 residues (91%) of tagged SRC-2 RID.
Protein: DP01880 (UniProt Q15596)
Region: residues 624	to 829
Annotation: protein binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Addition of PPARg-RXRa LBD heterodimer resulted in significant peak line broadening and disappearance of NMR peaks for residues within, flanking, and linking all three LXXLL motifs in SRC-2 RID. This indicates that all three LXXLL motifs are likely in direct contact with PPARg-RXRa.
Protein: DP01881 (UniProt P0C077)
Region: residues 85	to 95
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we present the crystal structure of the intact Escherichia coli RelB2E2 complex at 2.8 Å resolution, comprising both the RelB-inhibited RelE and the RelB dimerization domain that binds DNA.  The results thus provide a firm basis for understanding the model of conditional cooperativity at the molecular level.
The structure covers most of RelE (residues 2–80 of 95) and one molecule of RelB (residues 2–79 of 79), whereas the other two RelB molecules lack either the C terminus (residues 2–69) or N terminus (residues 33–79) due to poor electron density (Figure 1A). The flexible, C-terminal helix of RelE (helix α3, residues 85–95) is disordered in all molecules in this crystal form
Cross-references: PDB:4FXE
Protein: DP01881 (UniProt P0C077)
Region: residues 81	to 95
Annotation: disorder to order (Structural transition)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the free RelE(R81A/R83A) structure, helix alpha4 at the C terminus adopts a closed conformation contacting with the beta-sheet core and adjacent loops. In the RelE(R81A/R83A)-RelB(C) complex, helix alpha3(*) of RelB(C) displaces alpha4 of RelE(R81A/R83A) from the binding site on the beta-sheet core. This helix replacement results in neutralization of a conserved positively charged cluster of RelE by acidic residues from alpha3(*) of RelB. The released helix alpha4 becomes unfolded, adopting an open conformation with increased mobility

Our structures indicate that RelB counteracts the toxic activity of RelE by displacing alpha4 helix from the catalytically competent position found in the free RelE structure.

On the other hand, the chemical shift index analysis of RelER81A/R83A revealed an unfolding of a C-terminal helix (α4) coupled with RelBC binding (supplemental Fig. S3, C and D)
the C-terminal tail (Ala81-Leu95) in cyan [...] Comparison of RelBC-bound RelER81A/R83A to the unbound structure reveals a pronounced conformational change of α4 and adjacent loops (loop α3-β2 and β4-α4). The α4 swings out from the surface of the central β-sheet as it is displaced by the amphipathic helix α3* from RelBC in the complex (Figs. (Figs.33 and and4).4). The large chemical shift perturbation in the C-terminal tail region of RelER81A/R83A by RelBC is because of a conformational change rather than direct interaction (Fig. 2, A and C, and supplemental Fig. S4, A and B). The released α4 becomes unfolded, as evidenced by the chemical shift index analysis results (supplemental Fig. S3, C and D).[...] Upon binding of RelBC, RelER81A/R83A displays large changes in both the hetNOE and R2 values, especially around the C-terminal helix α4 region. A dramatic reduction in hetNOE and R2 values within the α4 region is observed, indicating an increase in the mobility of this region (supplemental Fig. S5, B and D).

Cross-references: PDB:2KC9
Protein: DP01881 (UniProt P0C077)
Region: residues 81	to 95
Annotation: toxin sequestering activity (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
In the free RelE(R81A/R83A) structure, helix alpha4 at the C terminus adopts a closed conformation contacting with the beta-sheet core and adjacent loops. In the RelE(R81A/R83A)-RelB(C) complex, helix alpha3(*) of RelB(C) displaces alpha4 of RelE(R81A/R83A) from the binding site on the beta-sheet core. This helix replacement results in neutralization of a conserved positively charged cluster of RelE by acidic residues from alpha3(*) of RelB. The released helix alpha4 becomes unfolded, adopting an open conformation with increased mobility

Our structures indicate that RelB counteracts the toxic activity of RelE by displacing alpha4 helix from the catalytically competent position found in the free RelE structure.


The perturbation of the proper arrangement of critical residues at an active site seems to be a common theme for the inactivation mechanism of RelE/ParE superfamily TA systems.  Our structural studies provide evidence that RelB antitoxin directly inhibits RelE toxin through binding to the active site, although the formation of a RelE2-RelB2 complex mediated through the N-terminal dimerization domain of RelB (16) may also spatially block RelE from entering the ribosomal A-site where the RNA cleavage takes place
Cross-references: PDB:2KC9
PDB:2KC8
Protein: DP01883 (UniProt P02655)
Region: residues 40	to 65
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The central region, comprising residues 40−65, is substantially disordered despite having a significant role in the activation of LpL.
Cross-references: PDB:1SOH
Protein: DP01883 (UniProt P02655)
Region: residues 40	to 65
Annotation: molecular function activator activity (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The central region, comprising residues 40−65, is substantially disordered despite having a significant role in the activation of LpL
Protein: DP01884 (UniProt Q9UKT5)
Region: residues 242	to 271
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
In the refined model, residues 161–163 of Skp1 and residues 132–135, 242–271, and 384–387 of Fbx4core were not visible in the electron density maps and are likely to be disordered.
Cross-references: PDB:3L2O
Protein: DP01887 (UniProt P08592)
Region: residues 672	to 687
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
After performing NMR experiments, the authors found nor the free nor the bound to Zn(+2) A-b peptides (1-16) (from the Amyloid beta-A4 region 672 to 687) have a regular structure but a serie of bend, coil and turn regions without regular secondary structure. In addition, they described a relatively fast (in NMR timescale) exchange between several conformational states, typical from an unstructured peptides/proteins.
Protein: DP01887 (UniProt P08592)
Region: residues 672	to 687
Annotation: zinc ion binding (Molecular function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The NMR spectra of free rat Ab(1–16) contain sharp signals typical of small monomeric peptides, but they become broader upon addition of Zn(2+). The observed changes in the spectra indicate the formation of a complex of rat Ab(1–16) with Zn(2+) ions.
Protein: DP01890 (UniProt Q07930)
Region: residues 1	to 51
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Apart from a long, flexible loop (residues 112–121), amino acids 52–204 could be modeled unequivocally
into the electron density map of full-length Pml1p. The remaining N-terminal part (residues1–51) could not be traced (...). This finding confirmed the results of our biochemical analyses, suggesting that the first 51 residues of Pml1p are unstructured in the isolated protein.
Protein: DP01890 (UniProt Q07930)
Region: residues 112	to 121
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Apart from a long, flexible loop (residues 112–121), amino acids 52–204 could be modeled unequivocally
into the electron density map of full-length Pml1p. The remaining N-terminal part (residues1–51) could not be traced (...). This finding confirmed the results of our biochemical analyses, suggesting that the first 51 residues of Pml1p are unstructured in the isolated protein.
Protein: DP01890 (UniProt Q07930)
Region: residues 22	to 42
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
NMR secondary chemical shifts for the free Pml1p (22-42)  clearly evidenced a disordered structure -no secondary structure tendency-.
Protein: DP01890 (UniProt Q07930)
Region: residues 1	to 61
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
Equilibrium CD spectra of Pml1p-(1– 61) were consistent with a random coil structure in this part of the protein (Fig. 3B). Thus, an intrinsically unstructured portion at the N terminus of Pml1p (residues 1– 61) is sufficient for interaction with Snu17p, reminiscent of the situation in Bud13p.
Protein: DP01898 (UniProt O60885)
Region: residues 333	to 349
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The amminoacid residues, 333-349, are missing in the crystallized structure, as is known from the PDB.


Cross-references: PDB:2OUO
Protein: DP01907 (UniProt Q13568)
Region: residues 458	to 467
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 458–467 were not visible in the electron density maps and are not included in the refined model
Cross-references: PDB:3DSH
Protein: DP01914 (UniProt Q96RI1)
Region: residues 275	to 290
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
the 15 residue insertion region between helices 1 and 3 is completely disordered in the FXR crystal structure.
Cross-references: PDB:1OSH
Protein: DP01921 (UniProt Q92900)
Region: residues 348	to 359
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
First, the regulatory loop of UPF12ΔCH is well ordered and folded into a 310 helix, whereas that of UPF11ΔCH is partially disordered and in an extended conformation.
Therefore, the extended loop of UPF11 points away from the helicase core and is oriented toward the solvent (Figure 4B, inset). Our structural observations suggest that the longer regulatory loop of UPF11 has a higher intrinsic flexibility than that of the regulatory loop of UPF12.
The shorter regulatory loop of UPF12ΔCH (in blue) is well ordered and folded into a 310 helix which is positioned toward the helicase core while the partially disordered longer loop of UPF11ΔCH (in cyan) is highly flexible and oriented toward the solvent.
Residues 348-359 are not visible in the electron density map.
Cross-references: PDB:6EJ5
Protein: DP01921 (UniProt Q92900)
Region: residues 348	to 359
Annotation: molecular function regulator (Molecular function)
Evidence: phosphatase assay evidence used in manual assertion
Supporting statements:
We compared the ATPase activities of UPF11 and UPF12 and found that a longer regulatory loop did not inhibit the catalytic activity of the helicase (Figure 1C, compare purple and yellow traces). In fact, UPF11 showed a marginally higher ATPase activity than UPF12.
Contrary to our expectations of stronger inhibition of catalytic activity by the long regulatory loop, we find that activated UPF11 shows significantly higher ATPase activity than activated UPF12 (Figure 2C, compare first two columns in the middle and right stacks). Furthermore, the ATPase activity of UPF11ΔCH is identical to that of the UPF1ΔCHΔloop mutant (Figure 2C, compare second and third column in the right stack), indicating that deletion or elongation of the regulatory loop mediates similar effects on the activity of UPF1.
Residues 348-359 are not visible in the electron density map and therefore this region is disordered within the regulatory loop (PDB: 6EJ5).
Protein: DP01921 (UniProt Q92900)
Region: residues 348	to 359
Annotation: molecular function regulator (Molecular function)
Evidence: experimental evidence used in manual assertion
Supporting statements:
We sought to determine whether presence of a longer regulatory loop in UPF1 would also mediate a similar effect on its RNA-binding affinity. To address this, we performed fluorescence anisotropy assays with UPF11ΔCH and UPF12ΔCH using a fluorescein-labeled 26-mer RNA, in the presence and absence of ATP. As previously reported, UPF12ΔCH shows a significant (18-fold) reduction in RNA-binding affinity in the presence of ATP while UPF11ΔCH shows only a modest 5-fold decrease (Figure 2D, compare cyan and green traces) (21,22). A similar trend was observed when comparing constructs encompassing the CH domain; UPF12 shows a 16-fold reduction in RNA-binding affinity in the presence of ATP in comparison to the 5-fold decrease exhibited by UPF11 (Figure 2D, compare purple and yellow traces). However, perturbing the length of the regulatory loop did not affect the length of RNA bound by UPF1 in the presence or absence of nucleotides, as observed in RNase protection assays (Supplementary Figure S2D and data not shown). Our results suggest that deletion or elongation of the regulatory loop modulates the RNA-binding affinity as well as the catalytic activity of UPF1 in a similar manner.
Residues 348-359 are not visible in the electron density map and therefore this region is disordered within the regulatory loop (PDB: 6EJ5).
Protein: DP01921 (UniProt Q92900)
Region: residues 348	to 359
Annotation: molecular function regulator (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
To determine the mechanistic basis of this differential catalytic activity, we have determined the X-ray crystal structure of the helicase core of UPF11 in its apo-state. Our results point toward a novel mechanism of regulation of RNA helicases, wherein alternative splicing leads to subtle structural rearrangements within the protein that are critical to modulate enzyme movements and catalytic activity.
The short regulatory loop of UPF12 is more rigid and occupies part of the RNA binding surface in the apo- and AMPPNP-bound states of UPF1. Therefore, it poses as a barrier to translocation of UPF1 upon ATP hydrolysis and has to be displaced from the RNA-binding pocket in each cycle (top panel). In contrast, the longer regulatory loop of UPF11 is flexible and does not effectively block RNA binding in the presence of ATP or impede translocation (bottom panel). As a consequence, this loop does not have to be removed from the RNA-binding surface each time to allow ATP-dependent translocation of UPF1, resulting in a more active helicase.
The regulatory loop of UPF11ΔCH approaches the RNA binding surface but does not significantly occlude it or clash with the RNA (inset), in comparison to the regulatory loop of UPF12ΔCH (Figure S1B).
Residues 348-359 are not visible in the electron density map.
Cross-references: PDB:6EJ5
Protein: DP01921 (UniProt Q92900)
Region: residues 348	to 359
Annotation: molecular function regulator (Molecular function)
Evidence: ATP bioluminescence assay evidence used in manual assertion
Supporting statements:
To assess whether the elongation of the regulatory loop has an impact on the properties of single molecules of UPF1, we compared the unwinding and translocation activities of UPF11ΔCH and UPF12ΔCH onto a long DNA hairpin.
However, UPF11ΔCH was two times faster than UPF12ΔCH with a weighted average rate of 2.4 bp/s during unwinding (1.0 bp/s for UPF12CH), and 4.6 bp/s during rezipping (2.4 bp/s for UPF12CH) (Figure 3 and Supplementary Figure S3). This result correlates perfectly with the higher ATP consumption rate of UPF11ΔCH compared to UPF12ΔCH (Figure 2C and Supplementary Figure S2C). Therefore, the recording of numerous and independent translocation events of single molecules of UPF1 revealed that its two natural isoforms possess different translocation speeds.
UPF11ΔCH unwinds nucleic acid with a higher translocation speed than UPF12ΔCH.
Residues 348-359 are not visible in the electron density map and therefore this region is disordered within the regulatory loop (PDB: 6EJ5).