General information | DisProt: | DP00182 | Name: | Major capsid protein VP1 | Synonym(s): | VP1_SV40
Major structural protein VP1
| First appeared in release: | Release 2.0 (02/14/2005) | UniProt: | P03087-1 | UniGene: | | SwissProt: | VP1_SV40 | TrEMBL: | | NCBI (GI): | 215274111 | Source organism: | Simian virus 40 (SV40) | Sequence length: | 362 | Percent disordered: | 48% | Homologues: | |
Native sequence |
10 20 30 40 50 60 | | | | | | MAPTKRKGSC PGAAPKKPKE PVQVPKLVIK GGIEVLGVKT GVDSFTEVEC FLNPQMGNPD - 60 EHQKGLSKSL AAEKQFTDDS PDKEQLPCYS VARIPLPNIN EDLTCGNILM WEAVTVKTEV - 120 IGVTAMLNLH SGTQKTHENG AGKPIQGSNF HFFAVGGEPL ELQGVLANYR TKYPAQTVTP - 180 KNATVDSQQM NTDHKAVLDK DNAYPVECWV PDPSKNENTR YFGTYTGGEN VPPVLHITNT - 240 ATTVLLDEQG VGPLCKADSL YVSAVDICGL FTNTSGTQQW KGLPRYFKIT LRKRSVKNPY - 300 PISFLLSDLI NRRTQRVDGQ PMIGMSSQVE EVRVYEDTEE LPGDPDMIRY IDEFGQTTTR - 360 MQ
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Functional narrative |
Function: Forms an icosahedral capsid with a T=7 symmetry and a 40 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with VP2 or VP3 proteins. Binds to N-glycolylneuraminic analog of the ganglioside GM1 on the cell surface to provide virion attachment to target cell. Once attached, the virion is internalized by caveolin-mediated endocytosis and traffics to the endoplasmic reticulum. Inside the endoplasmic reticulum, the protein folding machinery isomerizes VP1 interpentamer disulfide bonds, thereby triggering initial uncoating. Next, the virion uses the endoplasmic reticulum-associated degradation machinery to probably translocate in the cytosol before reaching the nucleus. Nuclear entry of the viral DNA involves the selective exposure and importin recognition of VP2/Vp3 nuclear localization signal. The assembly takes place in the cell nucleus. Encapsulates the genomic DNA and participates in rearranging nucleosomes around the viral DNA. The viral progenies exit the cells by lytic release.
Subunit structure: Homomultimer; disulfide-linked. The virus capsid is composed of 72 icosahedral units, each one composed of five disulfide-linked copies of VP1. Interacts with agnoprotein By similarity. Interacts with minor capsid proteins VP2 and VP3. Interacts with host HSPA8; this interaction probably participates in virus assembly. Interacts with host SP1; this interaction enhances the efficiency of viral packaging. Ref.7 Ref.8 Ref.10 Ref.13 Ref.15
Subcellular location: Virion. Host nucleus. Host endoplasmic reticulum. Note: Following host cell entry, the virion enters into the endoplasmic reticulum through a calveolar-dependent pathway. Then, viral DNA is translocated to the nucleus. Shortly after synthesis, a nuclear localization signal directs VP1 to the cell nucleus where virion assembly occurs.
Domain: The intrinsically disordered C-terminal region interacts with neighboring pentamers. The unstructured nature of this region allows to make different interactions depending on the stuctural context: pentamers present at the 12 icosahedral fivefold axes bind five pentamers, whereas pentamers present at the 60 icosahedral six-fold axes interact with six pentamers.
A DNA-binding domain overlapping a bipartite nuclear localization signal is present in the N-terminal region of the protein and is required for efficient virus formation.
Sequence similarities: Belongs to the polyomaviruses coat protein VP1 family.
(UniProt) ------------------------------------
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Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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Region 1 | Type: | Disordered | Name: | N-tail | Location: | 1 - 14 | Length: | 14 | Region sequence: |
MAPTKRKGSCPGAA | Modification type: | Native
| PDB: | | Structural/functional type: | Function arises from the disordered state | Functional classes: | | Functional subclasses: | | Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:See overall protein record comments (towards bottom of page) for additional information.
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N-terminal tail exhibited no density on x-ray, but likely resides at the base of the pentameric cone, consistent with most of the disorder for this protein.
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Region 2 | Type: | Disordered | Name: | N-arm and clamp | Location: | 15 - 89 | Length: | 75 | Region sequence: |
PKKPKEPVQVPKLVIKGGIEVLGVKTGVDSFTEVECFLNPQMGNPDEHQKGLSKSLAAEK QFTDDSPDKEQLPCY | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the disordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Structural mortar
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:Part of the jelly-roll beta-barrel, this region contains the N-arm and N-clamp that secures the "invading arm" from a different pentamer. According to Stehle et al (1996), this region may be unstructured in the absence of the invading arm's J-strands.
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See overall protein record comments (towards bottom of page) for additional information.
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Region 3 | Type: | Disordered | Name: | Loop CD | Location: | 90 - 107 | Length: | 18 | Region sequence: |
SVARIPLPNINEDLTCGN | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the disordered state | Functional classes: | Modification site
Molecular assembly
| Functional subclasses: | Phosphorylation
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:Loop CD differs in all six monomeric conformations, but contains five highly conserved residues at its tip. Of these five, T104 is a possible phosphorylation site and C105 forms a disulfide bridge with a neighboring pentamer. Since it resides inside the virion shell, at the base of the conical pentamer, Loop CD may interact with minor virion proteins VP2 and VP3 which also reside inside the shell.
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See overall protein record comments (towards bottom of page) for additional information.
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Region 4 | Type: | Ordered | Name: | Jelly-roll beta-barrel | Location: | 108 - 296 | Length: | 189 | Region sequence: |
ILMWEAVTVKTEVIGVTAMLNLHSGTQKTHENGAGKPIQGSNFHFFAVGGEPLELQGVLA NYRTKYPAQTVTPKNATVDSQQMNTDHKAVLDKDNAYPVECWVPDPSKNENTRYFGTYTG GENVPPVLHITNTATTVLLDEQGVGPLCKADSLYVSAVDICGLFTNTSGTQQWKGLPRYF KITLRKRSV | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the ordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Structural mortar
Substrate/ligand binding
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:This region represents the bulk of the jelly-roll beta-barrel (R2 and R7 contain additional beta-strands).
Loop DE (aa 122-148) inserts into the clockwise-neighboring monomer. Loop EF (aa 158-217) is found at the base of the pentameric cone. It includes a possible calcium binding site as well as beta-strands E', E" and E"'.
Strand G1 is contributed by the anticlockwise neighboring monomer. Strand G2 contains an important hairpin loop (aa 246-252).
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See overall protein record comments (towards bottom of page) for additional information.
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Region 5 | Type: | Disordered | Name: | Connector | Location: | 297 - 301 | Length: | 5 | Region sequence: |
KNPYP | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the disordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Flexible linkers/spacers
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:According to Stehle et al (1996), the connector is "completely conserved" and forms an "extended hinged link" that extends the "invading arm" forth to its target. There are three conformations of the connector, one of which Stehle et al describes as "not well-ordered."
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See overall protein record comments (towards bottom of page) for additional information.
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Region 6 | Type: | Disordered | Name: | Invading arm alphaC segment | Location: | 302 - 330 | Length: | 29 | Region sequence: |
ISFLLSDLINRRTQRVDGQPMIGMSSQVE | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises via a disorder to order transition | Functional classes: | Molecular assembly
| Functional subclasses: | Structural mortar
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:Part of the "invading arm," Region 6 contains the alphaC-helix that mediates interpentamer interaction via two- or three-helix bundles, or as in one monomeric conformation, is disordered. Also present is the "lid" (aa 321-328) that interacts with the N-terminal clamp of the invaded monomer.
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See overall protein record comments (towards bottom of page) for additional information.
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Region 7 | Type: | Disordered | Name: | Invading arm C-insert | Location: | 331 - 341 | Length: | 11 | Region sequence: |
EVRVYEDTEEL | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the disordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Structural mortar
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:Region 7 is the "C-insert" of the "invading arm," formed by Strands J and J', it nestles between Strands A and B of the invaded (target) monomer.
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See overall protein record comments (towards bottom of page) for additional information.
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Region 8 | Type: | Disordered | Name: | Invading arm C-terminal | Location: | 342 - 362 | Length: | 21 | Region sequence: |
PGDPDMIRYIDEFGQTTTRMQ | Modification type: | Complex
Native
| PDB: | 1SVA:1 | Structural/functional type: | Function arises from the disordered state | Functional classes: | Molecular assembly
| Functional subclasses: | Structural mortar
Substrate/ligand binding
Protein-protein binding
| Detection methods:
- X-ray crystallography
| References:
- Liddington RC, Yan Y, Moulai J, Sahli R, Benjamin TL, Harrison SC. "Structure of simian virus 40 at 3.8-A resolution." Nature. 1991; 354(6351): 278-84. PubMed: 1659663
- Stehle T, Gamblin SJ, Yan Y, Harrison SC. "The structure of simian virus 40 refined at 3.1 A resolution." Structure. 1996; 4(2): 165-82. PubMed: 8805523
| Comments:Region 8 is disordered in some monomers while in others it contains a hairpin loop. Contains a potential calcium binding site. This region is found at the base of the conical pentamer on the inside of the virion shell.
According to Stehle et al (1996), the "extreme part of the C-terminal intersects with the clockwise neighbor of the target [invaded] monomer."
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See overall protein record comments (towards bottom of page) for additional information.
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Comments |
Structure information from Stehle et al (1996) is based, in part, on Liddington et al (1991). PDB structure 1SVA is from Stehle et al and contains six identical chains.
Each VP1 pentamer consists of five monomers identical in amino acid sequence. Each monomer exhibits one of six different conformations depending upon its location in pentamer-to-pentamer interactions.
General structure of a monomer is a follows: disordered N-tail, N-terminal arm and "N-clamp", interior interaction loop, jelly-roll beta-barrel, connecting hinge, and an "invading arm" that consists of an interpentamer-mediating helix, a "lid" which interacts with an N-clamp, the "C-insert" beta strands and a C-terminal segment.
Structural disorder is concentrated towards the base of pentameric VP1's roughly conical shape, placing it inside the virion shell.
The jelly-roll beta-barrel is formed by two beta-sheets and includes beta-strands contributed by neighboring monomers: a six-stranded sheet (A, J, B, I, D, G2), Strand J is contributed by the "invading arm" of a different pentamer, and a five-stranded sheet (C, H, E, F, G1-), Strand G1- is from the anticlockwise neighboring monomer in the same pentamer.
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See additional comments included with individual regions.
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REGION CHANGE: With DisProt Release 6.0, regions for this protein have changed. Former Region 1 (aa I302-V329) is now part of Region 6, former Region 2 (aa D337-Q362) is now covered by Regions 7 and 8.
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