Structural highlights
Function
[VP1_POVMP] 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. Interacts with terminal alpha(2,3)-linked sialic acids on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through caveolin-mediated endocytosis. 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. In late phase of infection, neo-synthesized VP1 encapsulates replicated genomic DNA in the nucleus, and participates in rearranging nucleosomes around the viral DNA (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BACKGROUND: Murine polyomavirus recognizes (alpha2,3)-linked alpha-5-N-acetylneuraminic acid (sialic acid) on the surface of susceptible cells. While all strains bind to straight-chain receptors terminating in (alpha2,3)-linked sialic acid, some strains also bind to branched oligosaccharides that carry a second, (alpha2,6)-linked sialic acid. The ability to bind to these branched-chain receptors correlates with a single amino acid mutation at position 91 on the outer surface of the major capsid protein, VP1, and with a significant decrease in tumorigenicity. RESULTS: We have determined the structures of polyomavirus strain P16, which bears a glycine at position 91, in complex with model compounds for both straight-chain and branched-chain sialoglycoconjugates. The structures have been refined to a resolution of 3.65 degree. The ligands bind to a shallow groove on the surface of VP1. The sialic acid-(alpha2,3)-galactose moiety, which is common to both compounds, has specific and identical contacts. The additional (alpha2,6)-linked sialic acid moiety of the branched-chain receptor fragment fits into a surface pocket, but it has high thermal factors and does not form hydrogen bonds to groups on VP1. Data collected from crystals soaked at different oligosaccharide concentrations establish that both receptor fragments have similar, low affinities (dissociation constants in the range 5-10 mM) for the P16 virus, consistent with the interactions seen in the two complexes. CONCLUSION: The oligosaccharide-binding groove is complementary to the shape of the bound glycan, but there are relatively few hydrogen bonds between glycan and protein. Thus, the nature of the glycosidic linkages appears to be the principal determinant of specificity, rather than the position of particular hydroxyl groups. The low receptor affinity may be important for avoiding inhibition of viral release by retention on surface receptors of infected cells. Evidence suggests that strains with still greater pathogenicity are likely to have even weaker affinity.
Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments.,Stehle T, Harrison SC Structure. 1996 Feb 15;4(2):183-94. PMID:8805524[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stehle T, Harrison SC. Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments. Structure. 1996 Feb 15;4(2):183-94. PMID:8805524
