Structural basis for the receptor binding specificity of Norwalk virus

J Virol. 2008 Jun;82(11):5340-7. doi: 10.1128/JVI.00135-08. Epub 2008 Apr 2.

Abstract

Noroviruses are positive-sense, single-stranded RNA viruses that cause acute gastroenteritis. They recognize human histo-blood group antigens as receptors in a strain-specific manner. The structures presented here were analyzed in order to elucidate the structural basis for differences in ligand recognition of noroviruses from different genogroups, the prototypic Norwalk virus (NV; GI-1) and VA387 (GII-4), which recognize the same A antigen but differ in that NV is unable to bind to the B antigen. Two forms of the receptor-binding domain of the norovirus coat protein, the P domain and the P polypeptide, that were previously shown to differ in receptor binding and P-particle formation properties were studied. Comparison of the structures of the NV P domain with and without A trisaccharide and the NV P polypeptide revealed no major ligand-induced changes. The 2.3-A cocrystal structure reveals that the A trisaccharide binds to the NV P domain through interactions with the residues Ser377, Asp327, His329, and Ser380 in a mode distinct from that previously reported for the VA387 P-domain-A-trisaccharide complex. Mutational analyses confirm the importance of these residues in NV P-particle binding to native A antigen. The alpha-GalNAc residue unique to the A trisaccharide is buried deeply in the NV binding pocket, unlike in the structures of A and B trisaccharides bound to VA387 P domain, where the alpha-fucose residue forms the most protein contacts. The A-trisaccharide binding mode seen in the NV P domain complex cannot be sterically accommodated in the VA387 P domain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Dimerization
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Norwalk virus / chemistry*
  • Norwalk virus / genetics
  • Norwalk virus / metabolism*
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism*
  • Sensitivity and Specificity
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism

Substances

  • Oligosaccharides
  • Peptides
  • Receptors, Virus
  • Viral Proteins