LiteFold/DisProt huggingface dataset:
Protein: DP03591 (UniProt P38238)
Region: residues 213	to 232
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final model of apo-Trm7–Trm734 contained residues [Trm7 (chain B and D), 9–212 and 233– 259; Trm734 (chain A and C), 1–547, 555–758, 763–992, 997–1013], 310 water molecules, four SO42- molecules and two HEPES molecules, and the Trm7–Trm734–SAM complex contained residues [Trm7 (chain B and D), 9–212 and 233–259; Trm734 (chain A and C), 1–547, 555–758, 763– 992, 997–1013], 511 water molecules, 2 SAM molecules, 10 SO42- molecules and 2 HEPES molecules.
A structural model of two C-terminal regions of Trm7, W213- L232 and L260-V310, could not be built as these regions were not visible in the electron density (Figure 2B).
Cross-references: PDB:6JPL
PDB:6JP6
Protein: DP03591 (UniProt P38238)
Region: residues 260	to 310
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
The final model of apo-Trm7–Trm734 contained residues [Trm7 (chain B and D), 9–212 and 233– 259; Trm734 (chain A and C), 1–547, 555–758, 763–992, 997–1013], 310 water molecules, four SO42- molecules and two HEPES molecules, and the Trm7–Trm734–SAM complex contained residues [Trm7 (chain B and D), 9–212 and 233–259; Trm734 (chain A and C), 1–547, 555–758, 763– 992, 997–1013], 511 water molecules, 2 SAM molecules, 10 SO42- molecules and 2 HEPES molecules.
A structural model of two C-terminal regions of Trm7, W213- L232 and L260-V310, could not be built as these regions were not visible in the electron density (Figure 2B). The C-terminal region of L260-V310 was not degraded by contaminating proteases during the crystallization because we confirmed by SDS-PAGE analysis that Trm7 in the crystals retained its full length (data not shown). Therefore, the Cterminal region of Trm7 is disordered and likely to reside in the large space (Supplementary Figure S4).
The role of the disordered region (L260-V310) in Trm7 remains unclear because the region is invisible.
Cross-references: PDB:6JPL
PDB:6JP6
Protein: DP03591 (UniProt P38238)
Region: residues 260	to 310
Annotation: disorder (Structural state)
Evidence: small-angle X-ray scattering evidence used in manual assertion
Supporting statements:
We next performed SAXS analysis to confirm the Trm7–Trm734 heterodimeric complex structure in solution. As shown in Figure 2C, the structural model of Trm7–Trm734 with randomized loops (L260-V310) in the C-terminal Trm7 is superimposed well onto the envelope shape of the solution model generated from SAXS analysis, with good  2 and normalized spatial discrepancy (NSD) values (2.18 and 1.92, Supplementary Figure S5 and Table S4). Thus, these results confirm the heterodimer of the Trm7–Trm734 complex structure in solution as well as in the crystal and suggest the presence of a disordered C-terminal region (L260-V310) of Trm7.
Cross-references: SASBDB:SASDDR3
Protein: DP03592 (UniProt P03317)
Region: residues 1994	to 2006
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
Conversely, missing residues in SINV RdRp are located in N-terminal fingertips (index residues 91–103, flex residues 167–178, pinky residues 206–210, and ring residues 288–307) and C-terminus residues (residues 603–611) (Figure 2). The relatively large number of missing residues of the RRV RdRp structure suggests a highly dynamic structure which is also detected in the HDX measurement (see below, Figure 2).
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513. This evidence annotates the N-terminal fingertip: 1994-2006.
Cross-references: PDB:7VB4
Protein: DP03592 (UniProt P03317)
Region: residues 2070	to 2081
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
Conversely, missing residues in SINV RdRp are located in N-terminal fingertips (index residues 91–103, flex residues 167–178, pinky residues 206–210, and ring residues 288–307) and C-terminus residues (residues 603–611) (Figure 2). The relatively large number of missing residues of the RRV RdRp structure suggests a highly dynamic structure which is also detected in the HDX measurement (see below, Figure 2).
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513. This evidence annotates the flex residues: 2070-2081.
Cross-references: PDB:7VB4
Protein: DP03592 (UniProt P03317)
Region: residues 2191	to 2210
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
Conversely, missing residues in SINV RdRp are located in N-terminal fingertips (index residues 91–103, flex residues 167–178, pinky residues 206–210, and ring residues 288–307) and C-terminus residues (residues 603–611) (Figure 2). The relatively large number of missing residues of the RRV RdRp structure suggests a highly dynamic structure which is also detected in the HDX measurement (see below, Figure 2).
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513. This evidence annotates the ring residues: 2191-2210.
Cross-references: PDB:7VB4
Protein: DP03592 (UniProt P03317)
Region: residues 1989	to 2022
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513.
Protein: DP03592 (UniProt P03317)
Region: residues 1906	to 1958
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513.
Protein: DP03592 (UniProt P03317)
Region: residues 2053	to 2125
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
SINV nsP4FL corresponds to region 1904-2513 while its RdRp domain corresponds to region 1994-2513.
Protein: DP03593 (UniProt P13887)
Region: residues 2004	to 2053
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
The 83 mobile residues in RRV RdRp belong to the N-terminal fingertips and C-terminal thumb subdomains: index finger (residues 135–184; this flexible region is denoted as ‘flex’ region hereafter) (Figures 1, 2A, Supplementary Figures S2C and S3C), pinky, and ring fingers (residues 210–213 and 292–307, respectively) (Figure 2A and Supplementary Figure S2A), and C-terminus of the protein (residues 575–578, 588–593 and 600–611) (Figure 2A and Supplementary Figure S2B).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence annotates the index finger (‘flex’ region): 2004–2053.
Cross-references: PDB:7F0S
Protein: DP03593 (UniProt P13887)
Region: residues 2161	to 2176
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
The 83 mobile residues in RRV RdRp belong to the N-terminal fingertips and C-terminal thumb subdomains: index finger (residues 135–184; this flexible region is denoted as ‘flex’ region hereafter) (Figures 1, 2A, Supplementary Figures S2C and S3C), pinky, and ring fingers (residues 210–213 and 292–307, respectively) (Figure 2A and Supplementary Figure S2A), and C-terminus of the protein (residues 575–578, 588–593 and 600–611) (Figure 2A and Supplementary Figure S2B).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence annotates the ring finger: 2161–2176.
Cross-references: PDB:7F0S
Protein: DP03593 (UniProt P13887)
Region: residues 2469	to 2480
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Here, we report crystal structures of alphavirus RdRp from both RRV and SINV determined at 2.6 Å and 1.9 Å resolution respectively (Table 1). Having a dynamic structure, the RRV RdRp contains several disordered segments and some electron density in the RNA binding tunnel remains unassigned. The SINV RdRp adopts an overall fold similar to RRV RdRp but appears more ordered: residues that were disordered in the RRV nsP4 crystal structure are now well resolved in SINV RdRp and almost fully occupy the central RNA binding tunnel.
The 83 mobile residues in RRV RdRp belong to the N-terminal fingertips and C-terminal thumb subdomains: index finger (residues 135–184; this flexible region is denoted as ‘flex’ region hereafter) (Figures 1, 2A, Supplementary Figures S2C and S3C), pinky, and ring fingers (residues 210–213 and 292–307, respectively) (Figure 2A and Supplementary Figure S2A), and C-terminus of the protein (residues 575–578, 588–593 and 600–611) (Figure 2A and Supplementary Figure S2B).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence annotates the C-terminus: 2469-2480.
Cross-references: PDB:7F0S
Protein: DP03593 (UniProt P13887)
Region: residues 1870	to 1922
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
Based on the high D% HDX profile observed, the NTD of RRV nsP4FL appears quite flexible in solution, except at residues 53–74, where a predicted helix-loop-helix (HLH) substructure is located (Figure 2B–C). The linker between NTD and RdRp appears to have higher D% values, indicating increased dynamics in solution (Figure 2A).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03593 (UniProt P13887)
Region: residues 1943	to 1978
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
Based on the high D% HDX profile observed, the NTD of RRV nsP4FL appears quite flexible in solution, except at residues 53–74, where a predicted helix-loop-helix (HLH) substructure is located (Figure 2B–C). The linker between NTD and RdRp appears to have higher D% values, indicating increased dynamics in solution (Figure 2A).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence corresponds to the linker between NTD and RdRp.
Protein: DP03593 (UniProt P13887)
Region: residues 1943	to 1978
Annotation: flexible linker (Disorder function)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
Based on the high D% HDX profile observed, the NTD of RRV nsP4FL appears quite flexible in solution, except at residues 53–74, where a predicted helix-loop-helix (HLH) substructure is located (Figure 2B–C). The linker between NTD and RdRp appears to have higher D% values, indicating increased dynamics in solution (Figure 2A).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence corresponds to the linker between NTD and RdRp.
Protein: DP03593 (UniProt P13887)
Region: residues 1943	to 1978
Annotation: flexible linker (Disorder function)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Given its low molecular mass of 12.6 kDa, the recombinant NTD is amenable to structural characterization via NMR in solution. The NTD selected from RRV contains 107 amino acids with an expected number of 99 cross-peaks (excluding Pro residues) in the 1H-15N-HSQC spectrum. From these, ∼60 cross-peaks could be observed, making backbone resonance assignments challenging (Supplementary Figure S6). The narrow dispersion of the cross-peaks in the spectrum suggests that the NTD contains flexible and helical regions that support the NTD homology model and are in agreement with the HDX profile (Figure 2A, C and Supplementary Figure S6).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence corresponds to the linker between NTD and RdRp.
Protein: DP03593 (UniProt P13887)
Region: residues 1943	to 1978
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Given its low molecular mass of 12.6 kDa, the recombinant NTD is amenable to structural characterization via NMR in solution. The NTD selected from RRV contains 107 amino acids with an expected number of 99 cross-peaks (excluding Pro residues) in the 1H-15N-HSQC spectrum. From these, ∼60 cross-peaks could be observed, making backbone resonance assignments challenging (Supplementary Figure S6). The narrow dispersion of the cross-peaks in the spectrum suggests that the NTD contains flexible and helical regions that support the NTD homology model and are in agreement with the HDX profile (Figure 2A, C and Supplementary Figure S6).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479). This evidence corresponds to the linker between NTD and RdRp.
Protein: DP03593 (UniProt P13887)
Region: residues 1870	to 1922
Annotation: disorder (Structural state)
Evidence: nuclear magnetic resonance spectroscopy evidence used in manual assertion
Supporting statements:
Given its low molecular mass of 12.6 kDa, the recombinant NTD is amenable to structural characterization via NMR in solution. The NTD selected from RRV contains 107 amino acids with an expected number of 99 cross-peaks (excluding Pro residues) in the 1H-15N-HSQC spectrum. From these, ∼60 cross-peaks could be observed, making backbone resonance assignments challenging (Supplementary Figure S6). The narrow dispersion of the cross-peaks in the spectrum suggests that the NTD contains flexible and helical regions that support the NTD homology model and are in agreement with the HDX profile (Figure 2A, C and Supplementary Figure S6).
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03593 (UniProt P13887)
Region: residues 1870	to 1919
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03593 (UniProt P13887)
Region: residues 1946	to 2038
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03593 (UniProt P13887)
Region: residues 2071	to 2093
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03593 (UniProt P13887)
Region: residues 2429	to 2454
Annotation: disorder (Structural state)
Evidence: protein hydrogen-deuterium exchange mass spectrometry evidence used in manual assertion
Supporting statements:
A high percentage of deuteration (D%; hydrogen exchanged to deuterium) reflects the high solvent accessibility and flexibility of the regions on RRV and SINV nsP4.
RRV nsP4FL corresponds to region 1870-2479 (NTD: 1870-1978; RdRP: 1979-2479).
Protein: DP03594 (UniProt P50579)
Region: residues 1	to 109
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
HsMetAP-2, unlike EcMetAP- I and PfMetAP-2, has a 165-residue NH2-terminal extension, which is not essential for aminopeptidase activity (6). In the structure described here, the NH2-tenninal extension is largely disordered, and clear electron density begins at Lys110 with a disordered loop from residues 138 to 153 (Fig. 3B).
Residues 1-109 and 139-152 are disordered in the structures.
Cross-references: PDB:1B6A
PDB:1BOA
PDB:1BN5
Protein: DP03594 (UniProt P50579)
Region: residues 139	to 152
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
HsMetAP-2, unlike EcMetAP- I and PfMetAP-2, has a 165-residue NH2-terminal extension, which is not essential for aminopeptidase activity (6). In the structure described here, the NH2-tenninal extension is largely disordered, and clear electron density begins at Lys110 with a disordered loop from residues 138 to 153 (Fig. 3B).
Residues 1-109 and 139-152 are disordered in the structures.
Cross-references: PDB:1B6A
PDB:1BOA
PDB:1BN5
PDB:1B59
Protein: DP03595 (UniProt P53254)
Region: residues 1	to 80
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
N-terminal residues 1–80 of Utp22, C-terminal residues 190–297 of Rrp7, and several internal loops of each protein were not visible in the crystal structure, likely due to structural flexibility. SDS-PAGE analysis of dissolved crystals showed that Utp22 was intact and Rrp7 was partially degraded (unpublished data).
The current model contains Utp22 residues 81–274, 282–317, 326–445, 453–983, 1010 1116, and 1128–1237; Rrp7 residues 3–27, 32–105, and 120–189; 764 water molecules; 11 sulfate ions; and three PEG molecules.
Cross-references: PDB:4M5D
Protein: DP03595 (UniProt P53254)
Region: residues 984	to 1009
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
N-terminal residues 1–80 of Utp22, C-terminal residues 190–297 of Rrp7, and several internal loops of each protein were not visible in the crystal structure, likely due to structural flexibility. SDS-PAGE analysis of dissolved crystals showed that Utp22 was intact and Rrp7 was partially degraded (unpublished data).
The current model contains Utp22 residues 81–274, 282–317, 326–445, 453–983, 1010 1116, and 1128–1237; Rrp7 residues 3–27, 32–105, and 120–189; 764 water molecules; 11 sulfate ions; and three PEG molecules.
Cross-references: PDB:4M5D
Protein: DP03595 (UniProt P53254)
Region: residues 1117	to 1127
Annotation: disorder (Structural state)
Evidence: X-ray crystallography-based structural model with missing residue coordinates used in manual assertion
Supporting statements:
N-terminal residues 1–80 of Utp22, C-terminal residues 190–297 of Rrp7, and several internal loops of each protein were not visible in the crystal structure, likely due to structural flexibility. SDS-PAGE analysis of dissolved crystals showed that Utp22 was intact and Rrp7 was partially degraded (unpublished data).
The current model contains Utp22 residues 81–274, 282–317, 326–445, 453–983, 1010 1116, and 1128–1237; Rrp7 residues 3–27, 32–105, and 120–189; 764 water molecules; 11 sulfate ions; and three PEG molecules.
Cross-references: PDB:4M5D