LiteFold/DisProt huggingface dataset:
Protein: DP02637 (UniProt P07237)
Region: residues 348	to 357
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
PDI, also known as PDIA1, is the founding member and the most studied protein in the PDI family. PDI contains four thioredoxin‐like domains abb′a′, where a denotes catalytic domains containing CxxC motifs and b stands for non‐catalytic domains, with a 20‐residue x‐linker between b′ and a′ domain and a C‐terminal acidic tail.
The construct (residues 135–357) includes the bb′ domains and half of the x‐linker and yields high‐quality NMR spectra that were used to determine the NMR solution structure of the monomeric form
No electron density was observed for P135, E348–S357 (the x‐linker), the N‐terminal GPLGS cloning linker and, additionally, residues E323–L334 for chain A and E322–A336 for chain B that correspond to the strand β5 and β5–α4 loop in the b′x crystal structure.
Cross-references: PDB:4JU5
Protein: DP02637 (UniProt P07237)
Region: residues 479	to 508
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The highly acidic C-terminal region of PDI (residues 477–498) is also completely disordered and not seen in the electron density maps.
Cross-references: PDB:7ZSC
Protein: DP02638 (UniProt Q6ZPF4)
Region: residues 615	to 634
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A flexible linker of varying length allows considerable flexibility in orientation of the subunits
Cross-references: PDB:4EAH
Protein: DP02638 (UniProt Q6ZPF4)
Region: residues 615	to 634
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A flexible linker of varying length allows considerable flexibility in orientation of the subunits
The separation of actin subunits in the FMNL3–actin structure shows that each actin monomer can be held in place only through interactions with FH2 subunits, which suggests that flexibility in the FH2 linker region could allow the actin subunits to remain in contact with the FH2 domains while sliding past one another during elongation
Cross-references: PDB:4EAH
Protein: DP02639 (UniProt P78330)
Region: residues 45	to 56
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
For another 12 amino acids in MolA (45–56) and another ten amino acids in MolB (47–56), there is no visible density in the electron-density maps. As will be discussed later, this unfolded region coincides with the region that discriminates between the open and closed conformation.
Helix α3, connecting helix α2 to helix α4 in the closed conformation (not shown), is completely disordered in the open conformation and is therefore not visible.
Cross-references: PDB:1NNL
Protein: DP02639 (UniProt P78330)
Region: residues 45	to 56
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with high relative B-factor values used in manual assertion
Supporting statements:
For another 12 amino acids in MolA (45–56) and another ten amino acids in MolB (47–56), there is no visible density in the electron-density maps. As will be discussed later, this unfolded region coincides with the region that discriminates between the open and closed conformation.
The B-factor plot of the main-chain atoms, shown in Fig. 2, clearly indicates that the missing residues are located in a region of higher than average B factors.
Cross-references: PDB:1NNL
Protein: DP02640 (UniProt Q4F883)
Region: residues 35	to 52
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A flexible SAG101 segment between P35 and D52 is represented as a dotted line.
Cross-references: PDB:4NFU
Protein: DP02640 (UniProt Q4F883)
Region: residues 35	to 52
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A flexible SAG101 segment between P35 and D52 is represented as a dotted line.
Cross-references: PDB:4NFU
Protein: DP02641 (UniProt Q8GY88)
Region: residues 55	to 81
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
There are 28 residues preceding α-helix 1, which were not built in the AtSK2 structure due to a lack of corresponding electron density
Cross-references: PDB:3NWJ
Protein: DP02641 (UniProt Q8GY88)
Region: residues 212	to 227
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Most of the AtSK2 LID domain between α-helix 7 and α-helix 8 (residues 212-227) was not modeled in the AtSK2 crystal structure due to a lack of corresponding electron density. This region contains the substrate binding and putatively catalytic arginine (Arg117) of the LID domain
The apo-AtSK2 structure adopts the open conformation, as indicated by the orientation of the disordered LID domain away from the active site and the spacing of the ESB and NB domains away from the RC domain relative to the closed conformation MtSK structure.
The AtSK2 structure can be divided into four domains [Fig. 2(B)]: the reduced CORE (RC) domain comprising the central β-sheet and flanking α-helices, the nucleotide binding (NB) domain, which includes the phosphate binding loop (P-loop/Walker-A motif), the disordered LID domain, which contains catalytic and substrate binding residues, and the extended shikimate binding (ESB) domain, which includes a modified SK-type Walker B motif and several other substrate binding residues.
The extended loop region of the LID domain was not modeled in the AtSK2 structure.
Cross-references: PDB:3NWJ
Protein: DP02641 (UniProt Q8GY88)
Region: residues 212	to 227
Annotation: protein binding (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Most of the AtSK2 LID domain between α-helix 7 and α-helix 8 (residues 212-227) was not modeled in the AtSK2 crystal structure due to a lack of corresponding electron density. This region contains the substrate binding and putatively catalytic arginine (Arg117) of the LID domain
Cross-references: PDB:3NWJ
Protein: DP02641 (UniProt Q8GY88)
Region: residues 212	to 227
Annotation: molecular function regulator (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
Most of the AtSK2 LID domain between α-helix 7 and α-helix 8 (residues 212-227) was not modeled in the AtSK2 crystal structure due to a lack of corresponding electron density. This region contains the substrate binding and putatively catalytic arginine (Arg117) of the LID domain
Cross-references: PDB:3NWJ
Protein: DP02642 (UniProt P53780)
Region: residues 57	to 84
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The N-terminal domain (residues 57–131) is only partially defined (residues 57–84 are flexible) and interacts with the active site of the neighboring monomer.
hree stretches of the polypeptide chain were invisible in the electron density maps; the N-terminal part, i.e. residues 57 to 84; the region between residues 418 to 433; and the 11 amino acids of the C-terminalStrep-tag
Cross-references: PDB:1IBJ
Protein: DP02642 (UniProt P53780)
Region: residues 57	to 84
Annotation: molecular adaptor activity (Molecular function)
Evidence: x-ray crystallography evidence used in manual assertion
Supporting statements:
The N-terminal domain (residues 57–131) is only partially defined (residues 57–84 are flexible) and interacts with the active site of the neighboring monomer.
Three stretches of the polypeptide chain were invisible in the electron density maps; the N-terminal part, i.e. residues 57 to 84; the region between residues 418 to 433; and the 11 amino acids of the C-terminalStrep-tag
Cross-references: PDB:1IBJ
Protein: DP02643 (UniProt Q9MAB9)
Region: residues 101	to 116
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Disordered residues 101–116 of the C terminus have been omitted for clarity
Cross-references: PDB:1SE9
Protein: DP02644 (UniProt Q9SUM3)
Region: residues 263	to 303
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A hinge region links the N‐terminal FMN‐binding domain to the rest of CPR.
Two forms of ATR2 exist in the crystal. Form A (chain A) has the electron density for all four domains except a 43‐residue fragment of the hinge region; Form B (chain B) has the electron density for three domains, but lacks that for the FMN‐binding domain (Fig. 2A). The structure of ATR2 is described based on Form A unless noted otherwise.
Cross-references: PDB:5GXU
Protein: DP02644 (UniProt Q9SUM3)
Region: residues 263	to 303
Annotation: flexible linker (Disorder function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
A hinge region links the N‐terminal FMN‐binding domain to the rest of CPR.
Two forms of ATR2 exist in the crystal. Form A (chain A) has the electron density for all four domains except a 43‐residue fragment of the hinge region; Form B (chain B) has the electron density for three domains, but lacks that for the FMN‐binding domain (Fig. 2A). The structure of ATR2 is described based on Form A unless noted otherwise.
Cross-references: PDB:5GXU
Protein: DP02644 (UniProt Q9SUM3)
Region: residues 73	to 303
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Two forms of ATR2 exist in the crystal. Form A (chain A) has the electron density for all four domains except a 43‐residue fragment of the hinge region; Form B (chain B) has the electron density for three domains, but lacks that for the FMN‐binding domain (Fig. 2A). The structure of ATR2 is described based on Form A unless noted otherwise.
Disordered region in chain B that includes FMN-binding domain, solved in chain A, and hinge region (263-303) that is disordered in both chains
Cross-references: PDB:5GXU
Protein: DP02645 (UniProt Q9HC35)
Region: residues 45	to 64
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Only residues 14–44 were visible in the electron density map but most strikingly they formed a trimeric coiled-coil.
Cross-references: PDB:4CGC
Protein: DP02646 (UniProt P23457)
Region: residues 312	to 322
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final model contains 305 (residues 1−26, 30−221, and 225−311) out of 322 residues in the protein.
A β-hairpin seals the N-terminal end of the barrel (residues 7−17), while the C-terminus is a 23-residue coil, of which the last 11 residues are disordered.
Although chain breaks are not shown, portions of two loops (residues 27−29 and 222−224) are disordered, as are the C-terminal residues 312−322
Portions of two loops (residues 27−29 and 222−224) and the C-terminus (residues 312−322) were classified as disordered, and these residues were not included in the model.
Residues 27−29, 222−224, and 312−322 are disordered and were not included in the model.
Cross-references: PDB:1LWI
Protein: DP02647 (UniProt O95278)
Region: residues 69	to 79
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Residues 69–79 were 100% deuterated throughout the DXMS experiment, and these residues were disordered and not modeled in the structure (labeled disordered loop)
Cross-references: PDB:4RKK
Protein: DP02648 (UniProt Q8GXX0)
Region: residues 174	to 191
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The flexibility of the carboxy-terminal tail of AtErv1 in the crystal structure and the requirement for the shuttle disulfide in activity assays led us to speculate that the shuttle disulfide region may be modular and sufficient for substrate recognition.
When the carboxy-terminal 18 residues of AtErv1 were not seen in the electron density maps, we sought to determine if they were present in the crystals or if the protein had suffered proteolytic degradation during crystallization.
Nevertheless, the AtErv1 crystal structure provides further support for the general flexibility of shuttle disulfide regions of eukaryotic sulfhydryl oxidases and, coupled with mutagenesis, confirms that dynamic polypeptide segments determine the substrate specificities and reaction rates of the ERV/ALR sulfhydryl oxidases.
In addition, both have a second disulfide bond on a flexible loop or tail of the protein, positioned so that it can either approach the active-site disulfide or extend into solvent.
The AtErv1 shuttle disulfide is in a region of the structure that is disordered and thus apparently mobile and exposed. This feature may facilitate access of protein substrates to the shuttle disulfide.
Cross-references: PDB:2HJ3
Protein: DP02648 (UniProt Q8GXX0)
Region: residues 174	to 191
Annotation: molecular function regulator (Molecular function)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The flexibility of the carboxy-terminal tail of AtErv1 in the crystal structure and the requirement for the shuttle disulfide in activity assays led us to speculate that the shuttle disulfide region may be modular and sufficient for substrate recognition.
When the carboxy-terminal 18 residues of AtErv1 were not seen in the electron density maps, we sought to determine if they were present in the crystals or if the protein had suffered proteolytic degradation during crystallization.
Nevertheless, the AtErv1 crystal structure provides further support for the general flexibility of shuttle disulfide regions of eukaryotic sulfhydryl oxidases and, coupled with mutagenesis, confirms that dynamic polypeptide segments determine the substrate specificities and reaction rates of the ERV/ALR sulfhydryl oxidases.
The shuttle disulfide is required for oxidation of protein substrates by AtErv1
Although the location and context of this "shuttle" disulfide differs among family members, it is proposed to perform the same basic function of mediating electron transfer from substrate to the enzyme active site. We have determined by X-ray crystallography the structure of AtErv1, an ERV/ALR enzyme that contains a Cys-X4-Cys shuttle disulfide and oxidizes thioredoxin in vitro, and compared it to ScErv2, which has a Cys-X-Cys shuttle and does not oxidize thioredoxin at an appreciable rate. The AtErv1 shuttle disulfide is in a region of the structure that is disordered and thus apparently mobile and exposed. This feature may facilitate access of protein substrates to the shuttle disulfide. To test whether the shuttle disulfide region is modular and can confer on other enzymes oxidase activity toward new substrates, we generated chimeric enzyme variants combining shuttle disulfide and core elements from AtErv1 and ScErv2 and monitored oxidation of thioredoxin by the chimeras. We found that the AtErv1 shuttle disulfide region could indeed confer thioredoxin oxidase activity on the ScErv2 core. 
Cross-references: PDB:2HJ3
Protein: DP02649 (UniProt P01023)
Region: residues 690	to 728
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
At this point, the polypeptide enters the 39‐residue bait‐region segment (P690–T728), which is disordered.
Cross-references: PDB:4ACQ
Protein: DP02649 (UniProt P01023)
Region: residues 690	to 728
Annotation: molecular function regulator (Molecular function)
Evidence: combinatorial experimental and author inference evidence contained in single publication used in manual assertion
Supporting statements:
At this point, the polypeptide enters the 39‐residue bait‐region segment (P690–T728), which is disordered.
This intrinsic flexibility is in accordance with a function as a universal bait for endopeptidases that must be freely accessible and prepared to adapt to different types of active‐site cleft.
The α2M tetramer operates through a unique irreversible “venus flytrap” mechanism (Supporting Information, Figure S1a), which “entraps” proteinases in the inhibitor tetramer that remain still active against small substrates or inhibitors.1, 2 Entrapping results from large conformational changes elicited upon cleavage by the proteinase within a multitarget “bait region” and exposition of a buried cysteine–glutamine thioester bond located within a “thioester domain” (TED).
Protein: DP02649 (UniProt P01023)
Region: residues 683	to 700
Annotation: disorder (Structural state)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The α-macroglobulin bait region is located equivalently with resi
dues 666-706 in human α2-macroglobulin.
Upon incubation with chymotryspin two new NH2-terminal sequences, 1 (minor) and 2 (major) were seen (Table 2A). In an experiment where the incubation period was 5 min only sequence 2 was found (not shown), demonstrating that chymotrypsin primarly cleaves at Tyr(682)-Gly (numbering of human α2M), and that cleavage at Tyr(700)-Asn is secondary. As described above secondary cleavages were also identified at Tyr(693)-Val and at Leu(705)-Asn.
Although restrictions in motility do exist, residues 683-700 appear to constitute a highly flexible surface loop
Protein: DP02649 (UniProt P01023)
Region: residues 683	to 700
Annotation: limited proteolysis display site (Disorder function)
Evidence: cleavage assay evidence used in manual assertion
Supporting statements:
The α-macroglobulin bait region is located equivalently with resi
dues 666-706 in human α2-macroglobulin.
Although restrictions in motility do exist, residues 683-700 appear to constitute a highly flexible surface loop
The partial bait region sequence determined earlier (Sottrup-Jensen et al., 1984c) was completed by analyzing overlapping CNBr fragments and tryptic peptides obtained from PZP or the PZP-chymotrypsin complex (Figs.1-3 and Table 1)
Protein: DP02651 (UniProt P30542)
Region: residues 301	to 326
Annotation: disorder (Structural state)
Evidence: cryogenic electron microscopy-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The A1R transmembrane domain regions and extracellular and intracellular loops (ECL and ICL, respectively) are well defined, with the exception of 7 residues in ICL3 and the last 25 residues of helix 8.
Cross-references: PDB:6D9H
Protein: DP02652 (UniProt Q96FQ6)
Region: residues 51	to 71
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The structure generally shows a well-defined electron density map for the four helices of the two EF-hand motifs of each subunit except for residues from 51 to 71 of monomer D, comprising helix III and part of the loop between helix III and IV. This is consistent with a very high degree of mobility of these regions in the crystal lattice, as also indicated by the B factors.
Cross-references: PDB:3NXA
Protein: DP02653 (UniProt P61765)
Region: residues 295	to 358
Annotation: disorder to order (Structural transition)
Evidence: circular dichroism evidence used in manual assertion
Supporting statements:
We identified a conformational change in Munc18-1 domain 3a (residues 295–358); these residues form the predominant interaction site with Sx1 helices H3 and Hc in the Munc18-1–Sx1 closed structure (6). In that structure, Munc18-1 residues 295–358 form a bent hairpin, but in the Munc18-1 structure reported here the hairpin is unfurled, involving a 180° rotation and > 25 Å translation of backbone residues to form an extended antiparallel helical hairpin.
Munc18-1 domain 3a may be flexible in the unbound solution state and adopt an ordered conformation upon interaction with binding partners. We showed that a domain 3a peptide interacts with preformed SNARE complex, as evidenced by an increase in helicity consistent with coiled-coil formation.
Domain 3a variability suggests this region may be unstructured in the unbound solution state and possibly adopts a helical structure upon interaction with partners
Protein: DP02653 (UniProt P61765)
Region: residues 295	to 358
Annotation: disorder (Structural state)
Evidence: circular dichroism evidence used in manual assertion
Supporting statements:
Munc18-1 domain 3a may be flexible in the unbound solution state and adopt an ordered conformation upon interaction with binding partners. We showed that a domain 3a peptide interacts with preformed SNARE complex, as evidenced by an increase in helicity consistent with coiled-coil formation.
Domain 3a variability suggests this region may be unstructured in the unbound solution state and possibly adopts a helical structure upon interaction with partners
We used CD spectroscopy to analyze whether a peptide corresponding to this region of Munc18-1 (residues 326–359) could interact with the SNARE ternary complex (formed from Sx1 H3 helix, His-SNAP25, and VAMP2). The CD spectrum from the mixture of peptide and SNARE complex (Fig. 4D) reveals an increase in helicity of about 8% in comparison with the SNARE complex. We would expect an increase in helicity of 11% if all 34 peptide residues form coiled-coil interactions with the helical residues of the SNARE complex. These results indicate that the isolated domain 3a peptide interacts with the SNARE complex and that this interaction induces coiled-coil formation in the peptide.
Protein: DP02653 (UniProt P61765)
Region: residues 295	to 358
Annotation: protein binding (Molecular function)
Evidence: circular dichroism evidence used in manual assertion
Supporting statements:
Munc18-1 domain 3a may be flexible in the unbound solution state and adopt an ordered conformation upon interaction with binding partners. We showed that a domain 3a peptide interacts with preformed SNARE complex, as evidenced by an increase in helicity consistent with coiled-coil formation.
Domain 3a variability suggests this region may be unstructured in the unbound solution state and possibly adopts a helical structure upon interaction with partners
We identified a conformational change in Munc18-1 domain 3a (residues 295–358); these residues form the predominant interaction site with Sx1 helices H3 and Hc in the Munc18-1–Sx1 closed structure (6). In that structure, Munc18-1 residues 295–358 form a bent hairpin, but in the Munc18-1 structure reported here the hairpin is unfurled, involving a 180° rotation and > 25 Å translation of backbone residues to form an extended antiparallel helical hairpin.