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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-DISEASE VIRUS

Author
item CARVER, JOHN - UNIVERSITA DI UDINE-ITALY
item ESPOSITO, GENNARO - UNIVERSITA DI UDINE-ITALY
item VIGLINO, PAOLO - UNIVERSITA DI UDINE-ITALY
item FOGOLARI, FEDERICO - UNIVERSITA DI UDINE-ITALY
item GUICHARD, GILLES - INST DE BIOLOGIE-FRANCE
item BRIAND, JEAN - INST DE BIOLOGIE, FRANCE
item VAN REGENMORTEL, MARC-H - INST DE BIOLOGIE, FRANCE
item Brown, Fred
item MASCAGNI, PAOLO - DEPT PEPTIDE CHEM.-ITALY

Submitted to: Biopolymers
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: This study examined by nuclear magnetic resonance the structure of the highly immunogenic peptide corresponding to the loop on the virus particle and compared it with that of the D-amino acid peptide possessing the same serological specificity. Although the two peptides possess some structural similarities, they also have some distinct differences. This study will help to identify those portions of the peptides which are responsible for the biological properties they have in common.

Technical 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.