title: Structural comparison between retro-inverso and parent peptides: molecular basis for the biological activity of a retro-inverso analogue of the immunodominant fragment of VP1 coat protein from foot-and-mouth disease virus.
abstract: Antibodies induced against intact foot-and-mouth disease Virus (FMDV) particles bind to the retro-inverso analogue of fragment 141-159 of the viral coat protein VP1 of FMDV, variant A, equally well as to the parent peptide. A conformational investigation of this retro-inverso peptide was carried out by nmr spectroscopy and restrained molecular modeling in order to identify the structural basis for the antigenic mimicry between these retro-inverso and parent peptides. In 100% trifluoroethanol a well-defined left-handed alpha-helical region exists from residue 150 to residue 159, which is consistently present in all conformational families obtained from restrained modelling. A less-defined left-handed helical region is present in the tract 144-148, which is also consistent for all structures. Conformational flexibility exists about Gly149, which leads to two types of structures, either bent or linear. In the bent structures, a three-residue inverse tight turn is found, which can be classified as an inverse gamma-turn centered at Gly149. The overall structural features of the retro-inverso peptide are shown to be similar to those of the parent L-peptide. The two molecules, however, are roughly mirror images because they share inherently chiral secondary structure elements. By comparing these conformational conclusions with the x-ray structure of the Fab complex of a corresponding VP1 antigenic fragment, a rationale is proposed to account for the topological requirements of specific recognition that are implied by the equivalent antigenic activity of the natural and retro-inverso compounds.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche Università di Udine, Italy.
authors.forename: J A
authors.initials: JA
authors.lastname: Carver
authors.forename: G
authors.initials: G
authors.lastname: Esposito
authors.forename: P
authors.initials: P
authors.lastname: Viglino
authors.forename: F
authors.initials: F
authors.lastname: Fogolari
authors.forename: G
authors.initials: G
authors.lastname: Guichard
authors.forename: J P
authors.initials: JP
authors.lastname: Briand
authors.forename: M H
authors.initials: MH
authors.lastname: Van Regenmortel
authors.forename: F
authors.initials: F
authors.lastname: Brown
authors.forename: P
authors.initials: P
authors.lastname: Mascagni
mesh_terms: D000595:Amino Acid Sequence; D005537:Aphthovirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002213:Capsid / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation
chemical_list: D036022:Capsid Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C442501:VP1 protein, Foot-and-mouth disease virus