LiteFold/DisProt huggingface dataset:
Protein: DP04118 (UniProt O43665)
Region: residues 111	to 121
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Eleven amino acids within RGS10, including αVI, are disordered in the Gαi3-bound complex (Fig. S4A). 
Cross-references: PDB:2IHB
Protein: DP04118 (UniProt O43665)
Region: residues 10	to 31
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
This region lacks electron density in the PDB structure indicating it is disordered.  
Cross-references: PDB:2IHB
Protein: DP04119 (UniProt Q01105-2)
Region: residues 168	to 188
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron density of the residues between the β4-strand and α6-helix (residues 168–188) could not be observed (Fig. 2A), which suggests that the lower part of the earmuff domain is highly mobile in aqueous solution. 
Cross-references: PDB:2E50
Protein: DP04120 (UniProt O14775)
Region: residues 1	to 56
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of the class C orphan GPCR GPR158 (Q5T848) in complex with RGS7(P49802)-Gβ5(O14775) shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 1	to 69
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of the class C orphan GPCR GPR158 (Q5T848) in complex with RGS7(P49802)-Gβ5(O14775) shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 221	to 260
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of the class C orphan GPCR GPR158 (Q5T848) in complex with RGS7(P49802)-Gβ5(O14775) shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 362	to 388
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of the class C orphan GPCR GPR158 (Q5T848) in complex with RGS7(P49802)-Gβ5(O14775) shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 24	to 70
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of apo GPR158 shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWL
EMDB:31351
Protein: DP04121 (UniProt Q5T848)
Region: residues 221	to 261
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The electron microscopy of apo GPR158 shows that this protein region lacks electron density, indicating it is disordered.
Cross-references: PDB:7EWL
EMDB:31351
Protein: DP04121 (UniProt Q5T848)
Region: residues 512	to 524
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The disordered ICL2 (10 residues) and the cytoplasmic tip of TM3 in apo GPR158 becomes ordered upon binding of RGS7 (Fig. 5b and Supplementary Fig. 9q).
ICL2 residues are described in Fig. 5b.
Cross-references: PDB:7EWL
EMDB:31351
Protein: DP04121 (UniProt Q5T848)
Region: residues 512	to 524
Annotation: order (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The disordered ICL2 (10 residues) and the cytoplasmic tip of TM3 in apo GPR158 becomes ordered upon binding of RGS7 (Fig. 5b and Supplementary Fig. 9q).
ICL2 residues are described in Fig. 5b. 
Cross-references: PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 512	to 524
Annotation: disorder to order (Structural transition)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The disordered ICL2 (10 residues) and the cytoplasmic tip of TM3 in apo GPR158 becomes ordered upon binding of RGS7 (Fig. 5b and Supplementary Fig. 9q).
ICL2 residues are described in Fig. 5b.
Cross-references: PDB:7EWR
EMDB:31363
PDB:7EWL
EMDB:31351
Protein: DP04121 (UniProt Q5T848)
Region: residues 669	to 702
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
However, most of the cytoplasmic domain of GPR158 (residues 669 to 863) is disordered except for a coiled-coil (Ha and Hb) comprising 61 residues (Supplementary Figs. 4d and 9s).
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 764	to 863
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
However, most of the cytoplasmic domain of GPR158 (residues 669 to 863) is disordered except for a coiled-coil (Ha and Hb) comprising 61 residues (Supplementary Figs. 4d and 9s).
Cross-references: PDB:7EWP
EMDB:31360
PDB:7EWR
EMDB:31363
Protein: DP04121 (UniProt Q5T848)
Region: residues 669	to 710
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Segments lacking regular secondary structures and disordered regions are represented as solid lines and dotted lines, respectively.
The citation above is available in Supplementary Fig. 4c.
Cross-references: PDB:7EWL
EMDB:31351
Protein: DP04122 (UniProt P93343)
Region: residues 241	to 260
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure of tobacco 14-3-3c was solved by molecular replacement using phases from human 14-3-3ζ (Liu et al., 1995), and shows 235 from a total of 260 residues.
Cross-references: PDB:1O9D
PDB:1O9E
PDB:1O9F
PDB:1O9C
Protein: DP04123 (UniProt Q5HYA8)
Region: residues 1	to 36
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The orange dashed line indicates the invisible region in the structure, reflecting flexibility.
Cross-references: PDB:7FH1
EMDB:31584
Protein: DP04123 (UniProt Q5HYA8)
Region: residues 644	to 665
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The orange dashed line indicates the invisible region in the structure, reflecting flexibility.
Cross-references: PDB:7FH1
EMDB:31584
Protein: DP04123 (UniProt Q5HYA8)
Region: residues 793	to 827
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The orange dashed line indicates the invisible region in the structure, reflecting flexibility.
Cross-references: PDB:7FH1
EMDB:31584
Protein: DP04123 (UniProt Q5HYA8)
Region: residues 849	to 867
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The orange dashed line indicates the invisible region in the structure, reflecting flexibility.
Cross-references: PDB:7FH1
EMDB:31584
Protein: DP04124 (UniProt C1JEX5)
Region: residues 734	to 761
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
The DB domain (aa 734–761) at the C-terminus of TbRAP1639-761 forms a long and flexible loop (Supplementary Fig. 1b, left).
Cross-references: PDB:7XRW
Protein: DP04125 (UniProt P06702)
Region: residues 87	to 114
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
The majority of unassigned peaks are within the S100A9 disordered C-terminal tail, most of which are also unassigned in the wild-type hS100A9 structure (27).
Cross-references: PDB:7UI5
Protein: DP04126 (UniProt P95493)
Region: residues 662	to 673
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
A single NMR structure of RgpB-CTD (residues 674–736) was used as the starting model, with the N-terminal 15 residue His-tag and RgpB-CTD residues 662–673 kept unstructured. 
Cross-references: PDB:7PQ4
Protein: DP04127 (UniProt W1QJK4)
Region: residues 1	to 19
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
The protein consists of the structured β-barrel core (residues 22–172) and disordered N and C-terminal tails (residues 1–22 and 173–178) (see Fig. 3b). 
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 47	to 56
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 115	to 128
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 141	to 158
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 141	to 158
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 115	to 128
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04127 (UniProt W1QJK4)
Region: residues 47	to 56
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance evidence used in manual assertion
Supporting statements:
There are several loops which have increased internal mobility in the ps-ns time scale (Fig. 5a). Among them are the loop L12 (residues 50–59), the loop L45, which separates helix α4 and strand β5 (residues 118–131), and the residues 144–161 between strand β5 and helix α6, including helix α5 in the middle (see Fig. 4d).
Cross-references: PDB:6Q44
Protein: DP04128 (UniProt P15126)
Region: residues 1	to 43
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The extreme sensitivity of the N-terminal region of L5 (up to residue 44) in the 5 S RNP complex to chymotrypsin indicates that the predicted disorder in this region of L5 persists when the protein is bound to 5 S rRNA.
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The CD spectrum of httNT at 35 °C (Fig. 4A) and the 35 °C – 5 °C difference spectrum (not shown) lack strong secondary structure features, suggesting the absence of a stable structure. At the same time, deconvolution analysis of the 35 °C spectrum predicts significant α-helix (see legend, Fig. 4), consistent with projections based on amino acid sequence 23,35.
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The CD dichotomy was clarified by high resolution NMR analysis (Fig. 5), which strongly suggests the absence of stably folded structure. Two-dimensional proton TOCSY and NOESY NMR analyses show that httNT adopts predominantly unfolded, random-coil conformations, characterized by small spectral dispersion, small secondary chemical shifts, and strong sequential Hα(i)-HN(i+1) NOEs with few sequential HN(i)-HN(i+1) or medium-range NOEs.
Despite this slight propensity, there is clearly no stable α-helix in this peptide in solution under physiological conditions. Thus, in the absence of an expanded polyQ, httNT adopts a conformation lacking significant secondary and tertiary structural features, while at the same time being in a collapsed state.
Protein: DP04129 (UniProt P42858)
Region: residues 19	to 29
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The unstructured random coil portion of polyQ region (Gln389-Gln399) is shown on Fig 1d as a striped orange loop. The remaining carboxy-terminal polyQ region (Gln400-Gln404) is resolved in the extended loop conformation (Orange stick model).
(d) The complete structure of B molecule of Htt17Q-EX1 monomer from c95 crystal. The striped orange loops are for the random coil region between Gln389 and Gln399, which is invisible on the map.
Cross-references: PDB:3IOR
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 34
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
The availability of 1H, 15N, and 13C chemical shifts for various residues enables one to estimate the fractional populations of secondary structural elements in N17Q17. This analysis was initially accomplished using the Secondary Structure Propensity (SSP) program (68) with the 13C chemical shift values identified for the Cα and Cβ sites of the various residues as inputs, as it has been demonstrated before that these chemical shifts are more relevant for predicting secondary structure propensities of intrinsically disordered proteins.
At low pH, the N17Q17 ensemble of conformers exhibits a clear propensity for α-helical structures forming in the central region of the peptide. This trend changes as pH increases, culminating with a structurally disordered structure—even one exhibiting slight β-sheet propensity—at physiological pH.
To this end, the 13CO, 13Cα, and 13Cβ chemical shifts extracted from 3D BEST NMR experiments at low and neutral pH were fed into CS-ROSETTA; Figure 8 shows the lowest score structures that emerge from this program. As had been observed using SSP and PONDR, this approach also reveals a low pH α-helical structure in the core region of the peptide, between residues Leu14 and Gln26 (Figure 8a). Also in agreement with the SSP and PONDR calculations, CS-ROSETTA shows that N17 helicity is lost when moving to neutral pH, where two separate sets of CS-ROSETTA simulations reveal disordered, coiled conformations for the entire peptide (Figure 8b).
Cross-references: BMRB:26965
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 17
Annotation: disorder (Structural state)
Evidence: far-UV circular dichroism evidence used in manual assertion
Supporting statements:
The results presented above provide support for the hypothesis that Ac-Nt17-QN-Nme peptides become disordered as polyglutamine length increases. Before moving on to further analysis of the conformational characteristics and intermolecular associations of these constructs, we present an experimental assessment of α-helical content. We performed UV circular dichroism (CD) measurements on the Nt17 peptide and compared the estimates obtained from these experiments to those presented in Fig. 1a.
We conclude that 34% is a reasonable estimate of the helical content for the Nt17 peptide in aqueous solution at 298 K.
Protein: DP04129 (UniProt P42858)
Region: residues 39	to 88
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
We find that the relative error in the calculated ⟨EFRET⟩ values increases with increasing sequence separation of dyes. The relative errors are as high as 13%. Comparatively, a protein that is uniformly expanded shows a mean relative error that is typically less than 4%. (33) These results suggest that the scaling determined from the A60C dye pair underestimates the distance between dyes for the remaining dye pairs, and this underestimation increases for longer sequence separations. Such a result is consistent with the N-terminus being more compact than the C-terminus of Httex1, as would be expected if the polyQ domain adopts compact conformations, whereas the PR domain adopts expanded conformations.
(1) the general distance preferences are conserved across polyQ repeat lengths and dye positions; (2) the combination of Nt17 and polyQ domains adopt compact conformations as highlighted by small values for average distances between all pairs of residues within these domains; and (3) the PR domain predominantly adopts extended conformations, although there is a minor, temperature-dependent population characterized mainly by contacts between the flexible linker between polyproline modules of the PR domain and the surface of the polyQ domain (Supporting Information, Figure S6). Overall, these features suggest that Httex1 constructs adopt tadpole-like conformations for all polyQ repeat lengths. The tadpole-like architecture is defined by a globular “head”, consisting of Nt17 adsorbed to polyQ, and a semi-flexible “tail”, which refers to the PR domain.
(o) Two-dimensional histogram of Rg/N1/3 and δ for the polyQ-PR domains of Httex1 49Q. The red rectangle corresponds to the region that corresponds to globular conformations as defined above. For all polyQ lengths the probability of polyQ-PR domains adopting globular conformations is negligible.
We performed a similar analysis over polyQ-PR domains and found that for all polyQ lengths and dye pairs a negligible percentage of the conformations were observed to be globular. An example, two-dimensional histogram of Httex1 49Q is shown in Figure 4o. Most of the density was observed outside the region that corresponds to globular conformations.
Protein: DP04129 (UniProt P42858)
Region: residues 1	to 38
Annotation: disorder (Structural state)
Evidence: fluorescence resonance energy transfer evidence used in manual assertion
Supporting statements:
We find that the relative error in the calculated ⟨EFRET⟩ values increases with increasing sequence separation of dyes. The relative errors are as high as 13%. Comparatively, a protein that is uniformly expanded shows a mean relative error that is typically less than 4%. (33) These results suggest that the scaling determined from the A60C dye pair underestimates the distance between dyes for the remaining dye pairs, and this underestimation increases for longer sequence separations. Such a result is consistent with the N-terminus being more compact than the C-terminus of Httex1, as would be expected if the polyQ domain adopts compact conformations, whereas the PR domain adopts expanded conformations.
(1) the general distance preferences are conserved across polyQ repeat lengths and dye positions; (2) the combination of Nt17 and polyQ domains adopt compact conformations as highlighted by small values for average distances between all pairs of residues within these domains; and (3) the PR domain predominantly adopts extended conformations, although there is a minor, temperature-dependent population characterized mainly by contacts between the flexible linker between polyproline modules of the PR domain and the surface of the polyQ domain (Supporting Information, Figure S6). Overall, these features suggest that Httex1 constructs adopt tadpole-like conformations for all polyQ repeat lengths. The tadpole-like architecture is defined by a globular “head”, consisting of Nt17 adsorbed to polyQ, and a semi-flexible “tail”, which refers to the PR domain.
Figure 4m shows the results of the least-squares regression analysis for ln(N) versus ln(⟨Rg⟩). The parameters for the slope and intercept, obtained from the regression analysis, are found to be 0.36 and 2.62 Å, respectively. This implies that the polyQ domain maintains its intrinsic preference for globular conformations in the context of Httex1. These globular conformations are likely to be more stable as polyQ length increases because the surface-to-volume ratio decreases as N–1/3 as N increases.