title: A CD strategy for the study of polypeptide folding/unfolding. A synthetic foot-and-mouth disease virus immunogenic peptide.
abstract: The circular dichroism spectrum of the 20-residue immunogenic peptide from the foot-and-mouth disease virus (VP1; 141-160 of serotype A, subtype 12) was solvent- and temperature-dependent. Careful solvent titration revealed two isodichroic points and plateaux consistent with stepwise unfolding of specific stable conformations. Variable temperature studies in cryogenic solvents and urea perturbation were consistent with the existence of three conformational moieties, the left-handed extended helix, the alpha-helix, and the 3(10) helix. The number of residues in each helix was confirmed by CD spectral simulations. The strategy described here can be used to determine the components of a conformational equilibrium and their statistical weights, to study peptide folding and unfolding and to determine the bioactive conformation(s) of linear peptides. The conclusions were supported by 2D-NMR studies. A new mechanism for the stabilization of left-handed extended helices and destabilization of alpha-helices by urea is proposed. The structure of the peptide as resolved by CD spectroscopy is of particular significance since the conformation of this antigenic sequence in situ has so far not been solved by X-ray crystallography.
authors.affiliation: School of Pharmacy, Dept. of Pharmaceutical Chemistry, London, England.
authors.forename: G
authors.initials: G
authors.lastname: Siligardi
authors.forename: A F
authors.initials: AF
authors.lastname: Drake
authors.forename: P
authors.initials: P
authors.lastname: Mascagni
authors.forename: D J
authors.initials: DJ
authors.lastname: Rowlands
authors.forename: F
authors.initials: F
authors.lastname: Brown
authors.forename: W A
authors.initials: WA
authors.lastname: Gibbons
mesh_terms: D000595:Amino Acid Sequence; D005537:Aphthovirus / Q000737:chemistry / Q000276:immunology; D002213:Capsid / Q000737:chemistry* / Q000276:immunology; D036022:Capsid Proteins; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D012997:Solvents
chemical_list: D036022:Capsid Proteins; D000939:Epitopes; D010455:Peptides; D012997:Solvents