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Structure of Foot-and-mouth disease virus serotype A10₆₁ alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation

Wendy Blakemore^2,

Laura Miller^2,

¹ Division of Structural Biology, The Henry Wellcome Building for Genomic Medicine, Roosevelt Drive, Headington, Oxford OX3 7BN, UK
² Institute for Animal Health, Ash Road, Pirbright, Woking GU24 0NF, UK
³ Biophysics Section, The Blackett Laboratory, Imperial College, South Kensington Campus, London SW7 2AZ, UK
⁴ Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, UK

Correspondence
David I. Stuart
dave{at}strubi.ox.ac.uk

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 O₁BFS with heparin. The structure of FMDV A10₆₁ (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 A10₆₁ 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 O₁BFS, although the binding had a lower affinity and was more ionic.

Atomic coordinates have been deposited in the Protein Data Bank under accession codes 1ZBE and 1ZBA.

Present address: Astex Technology Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK.

Present address: Animal Health Research Unit, US Meat Animal Research Center, ARS USDA, PO Box 166, State Spur 18D, Clay Center, NE 68933, USA.

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