Structural basis for recognition of the HIV-1 V3 determinant by a neutralizing monoclonal antibody.

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

Structural basis for recognition of the HIV-1 V3 determinant by a neutralizing monoclonal antibody.

Int Conf AIDS. 1992 Jul 19-24;8(1):Mo13 (abstract no. MoA 0044). Unique Identifier : AIDSLINE ICA8/92400004
Profy A; Stura E; Stanfield R; Rini J; Fieser G; Silver S; Wilson I; Repligen Corp, Cambridge, MA.

Abstract: OBJECTIVE: Determine the structural requirements for recognition of the HIV-1 V3 neutralization determinant by a V3-directed monoclonal antibody. METHODS: Sequences recognized by the V3-directed neutralizing antibody R/V3-50.1 were determined using a panel of synthetic peptides. To better understand the interaction, the Fab fragment of the antibody was crystallized in a complex with the MN-derived synthetic peptide MP1 (KRIHIGPGRAFYTT). X-Ray diffraction data was collected at 2.8 A resolution and the crystal structure was solved using the molecular replacement method. A molecular model was built and refined using the sequences of the heavy and light chain variable domains. RESULTS: The conformation of the bound peptide and its contacts with the antibody are clearly revealed in the crystal structure. Consistent with immunochemical studies, the epitope includes the peptide sequence KRIHIG. The peptide is in van der Waals contact with residues in all six antibody CDR regions, and the isoleucine side chains are buried in the antigen binding pocket. CONCLUSIONS: The cocrystal structure provides a partial explantation for the observed sequence specificity of antibody R/V3 50.1. Knowledge of the V3-loop conformation recognized by this potent neutralizing antibody may aid in designing new vaccine candidates.

Keywords: Amino Acid Sequence Antibodies, Monoclonal/*IMMUNOLOGY Antibody Specificity Crystallization Epitopes/*IMMUNOLOGY Human HIV Antibodies/*IMMUNOLOGY HIV Envelope Protein gp120/*IMMUNOLOGY HIV-1/*IMMUNOLOGY Models, Molecular Molecular Sequence Data Peptide Fragments/*IMMUNOLOGY Protein Conformation X-Ray Diffraction ABSTRACT $KWDimmunologyproteinconformationx-raydiffractionabstract$
921230
M92C5343

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