Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment.
The polyomaviruses are non-enveloped, icosahedrally symmetrical particles with circular double-stranded DNA genomes. The outer shell of the virion contains 360 copies of viral protein VP1 (M(r) approximately 42K) arranged in pentamers. We report here the structure at 3.65 A resolution of murine polyomavirus ('polyoma') complexed with an oligosaccharide receptor fragment. This structure has been determined using the previously described model of simian virus 40 (SV40). Although very similar in structure to SV40, polyoma has interesting biological differences. Cell-surface N-acetyl neuraminic acid (sialic acid) is required for polyoma infectivity, but not for SV40. Polyoma attaches to the surface of susceptible cells by stereospecific recognition of oligosaccharides terminating in (alpha 2,3)-linked sialic acid. Studies of pathogenicity show that the specificity of viral binding to such oligosaccharides is an important determinant of the virus' ability to establish a disseminated infection and to induce tumours in the natural host. The complex described here show how polyoma recognizes the receptor fragment and how strains with different receptor specificities can distinguish between alternative ligands. The results also suggest an explanation for the large disparity in pathogenicity exhibited by strains differing in only one amino-acid residue of VP1.
Stehle
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Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138.
Yan
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Y
Benjamin
T L
TL
Harrison
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SC
D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D006386:Hemagglutination Tests; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid; D009844:Oligosaccharides / Q000737:chemistry*; D011120:Polyomavirus / Q000737:chemistry*; D011991:Receptors, Virus / Q000737:chemistry*; D012794:Sialic Acids / Q000737:chemistry; D013539:Simian virus 40 / Q000737:chemistry
D036022:Capsid Proteins; D009844:Oligosaccharides; D011991:Receptors, Virus; D012794:Sialic Acids; C062481:VP1 protein, polyomavirus; D019158:N-Acetylneuraminic Acid