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Title: THE SOLUTION STRUCTURE OF THE IMMUNODOMINANT AND CELL RECEPTOR BINDING REGIONS OF FMDV SEROTYPE A, VARIANT A

Author
item PEGNA, MONICA - ITALFARMACO RES CTR-ITALY
item MOLINARI, HENRIETTE - NMR LAB, MILAN, 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 SILIGARDI, GIULIANO - SCHOOL OF PHARMACY, UK
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: The structure of the immunodomdinant loop of FMDV has been analyzed by nuclear magnetic resonance. The objective of the work described in this paper was to obtain basic structural data on the loop from one isolate so that comparisons could then be made with other isolates which differ from it in antigenic properties although containing only single amino acid substitutions.

Technical Abstract: The solution structure of a 20 amino acid peptide (141-160 of protein VP1 from FMDV serotype A, variant A) has been determined by NMR experiments and computer calculations. The peptide contains both the immunodominant epitope as well as the cell receptor sequence RGD. These two sites have been shown to partially overlap. 135 NMR distance con- straints were used to obtain a set of 11 structures by distance geometry, minimization and molecular dynamics simulations. These structures were divided into 2 homogeneous families based upon backbone superimposition. The first and most populated family was characterized by a backbone RMS of 1.5 +/- 0.4 A, the second by a backbone RMS of 0.8 +/- 0.2 A. The two families differed mainly in the backbone angles of G149. In the larger of two families these angles favored the formation of a loop comprising residues 147-152 and stabilized by a H-bond between the NH of D147 and the CO of A152. In the 2nd family, where this bond was absent, the peptid adopted in this region the shape of an irregular helix. The C-terminal half the peptide (152-159) was similar in both families and largely helical. Similar structural features were also found within the VRGDS sequence (144-148) which was assigned to a B-turn, type IV. The features of the two families of structures were different from those of the recently published X-ray structure of the antigenic loop of a chemically modified form of FMDV. Proposals accounting for these differences are provided which take into account the dual activity of the 141-160 sequence (i.e. antibody binding and cell invasion through receptor binding).