The solution conformational features of two highly homologous antigenic peptides of foot-and-mouth disease virus serotype A, variant A and USA, correlate with their serological properties.

The solution structure of a peptide corresponding to the VP1 region 141-160 of foot-and-mouth disease virus (FMDV) serotype A variant USA has been studied by NMR and computer calculations and compared with the results from a study on a highly homologous peptide deriving from serotype A, variant A. The two peptides differ in their serological behavior and contain the immunodominant epitope of the virus which partly overlaps with its receptor binding region. Distance constraints, derived both from 2D and 3D homonuclear NMR and 2D-heteronuclear NMR experiments, were combined with DG calculations to yield 50 structures. After refinement through EM and restrained molecular dynamics simulations the selected structures shared several general features. In particular the 151-158 region was a helix in all cases while a large loop similar to that found in peptide A but comprising less residues and stabilized by an H-bond between the side chains of D147 and S150 was found in the majority of structures. A further loop, common to all structures, was identified around the RGD sequence (145-147). This was different from that found in the corresponding region of peptide A as were the conformations of the individual residues within the RGDX sequence. The different structural features shown by the two peptides were rationalized in terms of the S148 (peptide A) to F148 (peptide USA) mutation. The second mutation, that at position 153 (L in A, P in USA) did not appear to affect the structure of the peptide significantly although the different dimensions of the loop in the central region and the type of H-bond stabilizing it could be potentially ascribed to this second mutation. All criteria used pointed to different structural features for the two peptides consistent with their serological behaviour.