Conformational flexibility in a highly mobile protein loop of foot-and-mouth disease virus: Distinct structural requirements for integrin and antibody binding

Jordi X. Feliu, Antoni Benito, Baldomero Oliva, Francesc X. Avilés, Antonio Villaverde

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

The G-H loop of foot-and-mouth disease virus VP1 protein is a highly mobile peptide, that extends from the capsid surface and that in native virions is invisible by X-ray crystallography. In serotype C, this segment contains a hypervariable region with several continuous, overlapping, B-cell epitopes that embrace the conserved Arg-Gly-Asp (RGD) cell attachment motif. The solvent-exposed positioning of this peptide by selective insertion into different structural frameworks of E. coli β-galactosidase, generates a spectrum of antigenic variants which react distinctively with a panel of anti-VP1 monoclonal antibodies and exhibit different efficiencies as cell ligands. The cell attachment efficiency is much less restricted by the different positioning of the viral segment at the insertion sites. A molecular model of an inserted stretch reveals a highest flexibility of the RGD tripeptide segment compared with the flanking sequences, that could allow a proper accommodation to integrin receptors even in poorly antigenic conformations. The non-converging structural requirements for RGD-mediated integrin binding and antibody recognition, explains the dynamism of the generation of neutralisation-resistant antigenic variants in the viral quasi-species, arising from a conformational space of integrin-binding competent peptides. This might be of special relevance for foot-and-moth disease virus evolution, since unlike in other picornaviruses, the cell binding motif and the major neutralising B-cell epitopes overlap in a solvent-exposed peptide accessible to the host immune system, in a virion lacking canyons and similar hiding structures.
Original languageEnglish
Pages (from-to)331-338
JournalJournal of Molecular Biology
Volume283
DOIs
Publication statusPublished - 23 Oct 1998

Keywords

  • Antibody
  • FMDV
  • Integrin
  • Loop
  • RGD

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