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Title: THE SOLUTION CONFORMATIONAL FEATURES OF TWO HIGHLY HOMOLOGOUS ANTIGENIC PEPTIDES OF FMDV SEROTYPE A, VARIANTS A AND USA, CORRELATE WITH THEIR SEROLOGICAL PROPERTIES.

Author
item PEGNA, MONICA - ITALFARMACO RES CTR-ITALY
item MOLINARI, HENRIETTE - NMR LAB, MILIAN, ITALY
item ZETTA, LUCIA - NMR LAB, MILAN, ITALY
item GIBBONS, WILLIAM - UNIVERSITY OF LONDON, UK
item Brown, Fred
item ROWLANDS, DAVE - DEPT MOL SCI-WELLCOME, UK
item CHAN, E - ITALFARMACO RES CTR-ITALY
item MASCAGNI, PAOLO - ITALFARMACO RES CTR-ITALY

Submitted to: Journal of Peptide Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/29/1995
Publication Date: N/A
Citation: N/A

Interpretive Summary: A comparison was made of the structures of the immunodomdinant loops of two antigenic variants of FMDV. The two viruses could be readily distinguished by serological tests although differing at only two amino acid positions on the loop. The structural differences between the peptides corresponding to the two loops are centered on one of the substitutions; the second substitution apparently did not confer significant structural alteration.

Technical Abstract: The solution structure of a peptide corresponding to the VP1 region 141-160 of FMDV serotypes A, variant USA has been studied by NMR and computer calculations and compared with the results from a study on a highly homo- logous peptide deriving from serotype A, variant A. The two peptides differ in their serological behaviour and contain the immunodomdinant epitope of the virus which partly overlaps with its receptor binding region. Distanc constraints, derived both from 2D&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 o the peptide significantly although the different dimensions of the loop in the central region and the type of H-bond stabilizing it could be potential ascribed to this second mutation. All criteria used pointed to different structural features for the two peptides consistent with their serological behaviour.