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Data from cryo-electron microscopy and X-ray crystallography have been combined to study the interactions of foot-and-mouth disease virus serotype C (FMDV-C) with a strongly neutralizing monoclonal antibody (mAb) SD6. The mAb SD6 binds to the long flexible GH-loop of viral protein 1 (VP1) which also binds to an integrin receptor. The structure of the virus-Fab complex was determined to 30 A resolution using cryo-electron microscopy and image analysis. The known structure of FMDV-C, and of the SD6 Fab co-crystallized with a synthetic peptide corresponding to the GH-loop of VP1, were fitted to the cryo-electron microscope density map. The SD6 Fab is seen to project almost radially from the viral surface in an orientation which is only compatible with monovalent binding of the mAb. Even taking into account the mAb hinge and elbow flexibility, it is not possible to model bivalent binding without severely distorting the Fabs. The bound GH-loop is essentially in what has previously been termed the 'up' position in the best fit Fab orientation. The SD6 Fab interacts almost exclusively with the GH-loop of VP1, making very few other contacts with the viral capsid. The position and orientation of the SD6 Fab bound to FMDV-C is in accord with previous immunogenic data.

Original publication

DOI

10.1093/emboj/16.7.1492

Type

Journal article

Journal

EMBO J

Publication Date

01/04/1997

Volume

16

Pages

1492 - 1500

Keywords

Antibodies, Monoclonal, Antibodies, Viral, Antigens, Viral, Aphthovirus, Binding Sites, Capsid, Capsid Proteins, Computer Graphics, Freezing, Immunoglobulin Fab Fragments, Integrins, Microscopy, Electron, Models, Molecular, Protein Conformation, Protein Structure, Secondary