Mar 21, 2008

Structural basis of GM1 ganglioside recognition by simian virus 40

Proceedings of the National Academy of Sciences of the United States of America
Ursula NeuThilo Stehle

Abstract

Simian virus 40 (SV40) has been a paradigm for understanding attachment and entry of nonenveloped viruses, viral DNA replication, and virus assembly, as well as for endocytosis pathways associated with caveolin and cholesterol. We find by glycan array screening that SV40 recognizes its ganglioside receptor GM1 with a quite narrow specificity, but isothermal titration calorimetry shows that individual binding sites have a relatively low affinity, with a millimolar dissociation constant. The high-resolution crystal structure of recombinantly produced SV40 capsid protein, VP1, in complex with the carbohydrate portion of GM1, reveals that the receptor is bound in a shallow solvent-exposed groove at the outer surface of the capsid. Through a complex network of interactions, VP1 recognizes a conformation of GM1 that is the dominant one in solution. Analysis of contacts provides a structural basis for the observed specificity and suggests binding mechanisms for additional physiologically relevant GM1 variants. Comparison with murine Polyomavirus (Polyoma) receptor complexes reveals that SV40 uses a different mechanism of sialic acid binding, which has implications for receptor binding of human polyomaviruses. The SV40-GM1 complex reve...Continue Reading

Mentioned in this Paper

Biochemical Pathway
Conserved Sequence
Endocytosis
Ganglioside receptor
Complex (molecular entity)
Simian virus 40
Protein Structure, Quaternary
Procholeragenoid
Caveolin 1
Capsid

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