title: Structure of Foot-and-mouth disease virus serotype A10 61 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation.
abstract: Foot-and-mouth disease viruses (FMDVs) target epithelial cells via integrin receptors, but can acquire the capacity to bind cell-surface heparan sulphate (or alternative receptors) on passage in cell culture. Vaccine viruses must be propagated in cell culture and, hence, some rationale for the selection of variants in this process is important. Crystal structures are available for type O, A and C viruses and also for a complex of type O strain O(1)BFS with heparin. The structure of FMDV A10(61) (a cell culture-adapted strain) complexed with heparin has now been determined. This virus has an RGSD motif in place of the otherwise conserved RGD integrin-binding motif and the potential to bind heparan sulphate (suggested by sequence analyses). FMDV A10(61) was closely similar in structure to other serotypes, deviating most in antigenic sites. The VP1 GH loop comprising the integrin-binding motif was disordered. Heparin bound at a similar site and in a similar conformation to that seen in the analogous complex with O(1)BFS, although the binding had a lower affinity and was more ionic.
authors.affiliation: Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Fry
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: John W I
authors.initials: JWI
authors.lastname: Newman
authors.affiliation: Biophysics Section, The Blackett Laboratory, Imperial College, South Kensington Campus, London SW7 2AZ, UK.|Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Curry
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Saloua
authors.initials: S
authors.lastname: Najjam
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Terry
authors.initials: T
authors.lastname: Jackson
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Blakemore
authors.affiliation: Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lea
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Miller
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Burman
authors.affiliation: Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK.
authors.forename: Andrew M Q
authors.initials: AMQ
authors.lastname: King
authors.affiliation: Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK.
authors.forename: David I
authors.initials: DI
authors.lastname: Stuart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D018360:Crystallography, X-Ray; D029544:Foot-and-Mouth Disease Virus / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D006497:Heparan Sulfate / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D012703:Serotyping; D020349:Surface Plasmon Resonance
chemical_list: D006497:Heparan Sulfate; D009844:Oligosaccharides; D011991:Receptors, Virus