title: Structural basis for the recognition of Lewis antigens by genogroup I norovirus.
abstract: Noroviruses (NoVs) bind to histo-blood group antigens, namely, ABH antigens and Lewis antigens. We previously showed the NoVs GI/2, GI/3, GI/4, and GI/8 were able to strongly bind to Lewis a (Le(a)) antigen, which is expressed by individuals who are nonsecretors. In this study, to investigate how Lewis antigens interact with GI NoV virion protein 1 (VP1), we determined the crystal structures of the P domain of the VP1 protein from the Funabashi 258 (FUV258) strain (GI/2) in complexes with Le(a), Le(b), H type 1, or A type 1 antigens. The structures were compared with those of the NV/68 strain (GI/1), which does not bind to the Le(a) antigen. The four loop structures, loop P, loop S, loop A, and loop B, continuously deviated by more than 2 Å in length between the Cα atoms of the corresponding residues of the FUV258 and NV/68 P domains. The most pronounced differences between the two VP1 proteins were observed in the structures of loop P. In the FUV258 P domain, loop P protruded toward the next protomer, forming a Le(a) antigen-binding site. The Gln389 residue make a significant contribution to the binding of the Le(a) antigen through the stabilization of loop P as well as through direct interactions with the α4-fucosyl residue (α4Fuc) of the Le(a) antigen. Mutation of the Gln389 residue dramatically affected the degree of binding of the Lewis antigens. Collectively, these results suggest that loop P and the amino acid residue at position 389 affect Lewis antigen binding.
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kubota
authors.forename: Akiko
authors.initials: A
authors.lastname: Kumagai
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ito
authors.forename: Sanae
authors.initials: S
authors.lastname: Furukawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Someya
authors.forename: Naokazu
authors.initials: N
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Ishii
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Haruko
authors.initials: H
authors.lastname: Shirato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D007983:Lewis Blood Group Antigens / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009036:Moths; D009154:Mutation; D029322:Norovirus / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*
chemical_list: D007983:Lewis Blood Group Antigens; D011991:Receptors, Virus; D014764:Viral Proteins