9HV9

Crystal structure of Fab34 complexed with a 7-mer peptide of FMDV VP1

Summary for 9HV9

• Entry DOI: 10.2210/pdb9hv9/pdb
• Related: 9HV1 9HV2 9HV8
• Descriptor: heavy chain, light chain, Capsid protein VP1, ... (8 entities in total)
• Functional Keywords: foot-and-mouth disease virus, cattle antibody, cross-reactive, linear epitope, antibody structure, immune system
• Biological source: Bos taurus; More
• Total number of polymer chains: 3
• Total formula weight: 49898.27

Authors

Ren, J.,Duyvesteyn, H.M.E.,Stuart, D.I. (deposition date: 2024-12-24, release date: 2026-01-14, Last modification date: 2026-06-03)

Primary citation

Bonnet-Di Placido, M.,Duyvesteyn, H.M.E.,Steyn, A.W.,Hay, A.L.,Porta, C.,Valdez, K.R.,Lokhman, E.,Crossley, S.,Hanson, K.,Mwangi, W.N.,Munir, D.,Perez-Martin, E.,Knowles, N.J.,Burman, A.,Yassin, A.A.,Asfor, A.,Faralla, C.,Lam, K.J.,McComb, R.,Leifeld, C.,Pietersz, K.,King, D.P.,van den Born, E.,Duncan, S.K.,Charleston, B.,Fry, E.E.,Ren, J.,Stuart, D.I.,Hammond, J.A.
Cattle antibodies identify a cross-serotype broadly neutralising foot-and-mouth disease virus epitope.
Npj Vaccines, 11:-, 2026

PubMed Abstract: Foot-and-mouth disease virus (FMDV) causes a devastating disease that threatens global food security. Vaccination is hindered by antigenic diversity across serotypes. To identify cross-serotype neutralising epitopes, we isolated 24 FMDV-specific antibodies from cattle sequentially vaccinated with antigens from four serotypes, of which three neutralised three vaccine strains. These three antibodies neutralised 21 and bound 59 additional topotypes across O, A, Asia 1, and C serotypes. Cryo-EM complexes of Fabs with FMD virus-like particles indicated all three recognise a common flexible epitope at the VP1 C-terminus, confirmed by binding competition. Crystallography and structural modelling revealed that a normally inaccessible surface of the hydrophobic VP1 C-terminal peptides inserts into a similar groove in all three antibodies. Comparison of neutralisation activity and integrin receptor blocking by whole antibodies, F(ab')s, and Fabs suggests neutralisation is mediated by Fc steric hindrance of receptor binding. This cryptic, linear, and cross-serotype neutralising epitope may inform improved FMD vaccines.

PubMed: 41927576
DOI: 10.1038/s41541-026-01427-7

Experimental method

X-RAY DIFFRACTION (1.8 Å)