title: Structures of B-lymphotropic polyomavirus VP1 in complex with oligosaccharide ligands.
abstract: B-Lymphotropic Polyomavirus (LPyV) serves as a paradigm of virus receptor binding and tropism, and is the closest relative of the recently discovered Human Polyomavirus 9 (HPyV9). LPyV infection depends on sialic acid on host cells, but the molecular interactions underlying LPyV-receptor binding were unknown. We find by glycan array screening that LPyV specifically recognizes a linear carbohydrate motif that contains α2,3-linked sialic acid. High-resolution crystal structures of the LPyV capsid protein VP1 alone and in complex with the trisaccharide ligands 3'-sialyllactose and 3'-sialyl-N-acetyl-lactosamine (3SL and 3SLN, respectively) show essentially identical interactions. Most contacts are contributed by the sialic acid moiety, which is almost entirely buried in a narrow, preformed cleft at the outer surface of the capsid. The recessed nature of the binding site on VP1 and the nature of the observed glycan interactions differ from those of related polyomaviruses and most other sialic acid-binding viruses, which bind sialic acid in shallow, more exposed grooves. Despite their different modes for recognition, the sialic acid binding sites of LPyV and SV40 are half-conserved, hinting at an evolutionary strategy for diversification of binding sites. Our analysis provides a structural basis for the observed specificity of LPyV for linear glycan motifs terminating in α2,3-linked sialic acid, and links the different tropisms of known LPyV strains to the receptor binding site. It also serves as a useful template for understanding the ligand-binding properties and serological crossreactivity of HPyV9.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Neu
authors.forename: Zaigham Mahmood
authors.initials: ZM
authors.lastname: Khan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schuch
authors.forename: Angelina S
authors.initials: AS
authors.lastname: Palma
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Ten
authors.initials: T
authors.lastname: Feizi
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D036022:Capsid Proteins / Q000737:chemistry* / Q000276:immunology; D002236:Carbohydrate Conformation; D003429:Cross Reactions; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000276:immunology; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology; D011120:Polyomavirus / Q000737:chemistry* / Q000276:immunology; D013539:Simian virus 40 / Q000737:chemistry / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D009844:Oligosaccharides; C062481:VP1 protein, polyomavirus; D019158:N-Acetylneuraminic Acid