Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments

摘要: Abstract Background: Murine polyomavirus recognizes ( α 2,3)-linked -5- N -acetylneuraminic acid (sialic acid) on the surface of susceptible cells. While all strains bind to straight-chain receptors terminating in sialic acid, some also branched oligosaccharides that carry a second, 2,6)-linked acid. The ability these branched-chain correlates with single amino mutation at position 91 outer major capsid protein, VP1, and significant decrease tumorigenicity. Results We have determined structures strain P16, which bears glycine 91, complex model compounds for both sialoglycoconjugates. been refined resolution 3.65 a. ligands shallow groove VP1. acid-( 2,3)-galactose moiety, is common compounds, has specific identical contacts. additional moiety receptor fragment fits into pocket, but it high thermal factors does not form hydrogen bonds groups Data collected from crystals soaked different oligosaccharide concentrations establish fragments similar, low affinities (dissociation constants range 5–10mM) P16 virus, consistent interactions seen two complexes. Conclusion oligosaccharide-binding complementary shape bound glycan, there are relatively few between glycan protein. Thus, nature glycosidic linkages appears be principal determinant specificity, rather than particular hydroxyl groups. affinity may important avoiding inhibition viral release by retention infected Evidence suggests still greater pathogenicity likely even weaker affinity.