ISSN:
1075-2617
Keywords:
FMDV
;
structure
;
NMR spectrocopy
;
NEO constraints
;
RGD (Arg-Gly-Asp)
;
Chemistry
;
Biochemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The solution structure of a 20 amino acid long peptide corresponding to the region 141-160 of the envelope protein Vp1 from foot-and-mouth disease virus (FMDV) serotype A, variant A, has been determined by a combination of NMR experiments and computer calculations. The peptide contains both the immunodominant epitope as well as the sequence (RGD) used by the virus to bind the cell receptor in the initial stages of infection. These two sites have been shown to partially overlap.One hundred and thirty-five NMR distance constraints were used to obtain a set of 11 structures by distance geometry, minimization and molecular dynamics simulations. These structures were divided into two homogeneous families based upon backbone superimposition. The first and most populated family was characterized by a backbone RMS of 1.5±0.4 Å, the second by a backbone RMS of 0.8±0.2 Å. The two families had similar structural features and differed mainly in the backbone angles of G149. In the larger of the two families these angles favoured the formation of a loop comprising residues 147 to 152 and stabilized by a H-bond between the NH of D147 and the CO of A152. In the second family, where this bond was absent, the peptide adopted in this region the shape of an irregular helix. The C-terminal half of 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 β-turn type IV. The features of the two families of structures were found to be 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).
Additional Material:
11 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/psc.49
