Structural and functional characterization of an epitope in the conserved C-terminal region of HIV-1 gp120.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Structural and functional characterization of an epitope in the conserved C-terminal region of HIV-1 gp120.

J Pept Res. 1999 Jul;54(1):32-42. Unique Identifier : AIDSLINE MED/99376198
Ferrer M; Sullivan BJ; Godbout KL; Burke E; Stump HS; Godoy J; Golden A; Profy AT; van Schravendijk MR; Department of Molecular and Cellular Biology, Harvard University,; Cambridge, MA 02138, USA.

Abstract: Through an integrated study of the reactivity of a monoclonal antibody, 803-15.6, with synthetic peptides and native recombinant HIV-1 envelope glycoprotein gp120, we have obtained structure-functional information on a region of rgp120 not yet elucidated by X-ray crystallography. mAb 803-15.6 binds with high affinity and broad cross-clade specificity to the conserved C-terminal region (amino acids 502-516) of HIV-1 rgp120. Phage display selection from a random peptide library identified the core binding motif as AXXKXRH, homologous to residues 502-508. Using quantitative binding analyses, the affinity of mAb 803-15.6 for native, monomeric recombinant gp120HXB2 (rgp120) was found to be similar to that for the synthetic gp120 peptide (502-516). Circular dichroism studies indicate that the synthetic peptide largely has a random coil conformation in solution. The results therefore suggest that the 803-15.6 epitope is fully accessible on rgp120 and that this region of rgp120 is as flexible as the synthetic peptide. Residues 502-504 are on the edge of a putative gp41 binding site that has been postulated to change conformation on CD4 binding. However, the affinity of mAb 803-15.6 for rgp120 is not affected by binding of CD4 and vice-versa. These results suggest either that the 502-504 region does not change conformation upon CD4 binding, or that recombinant gp120 does not undergo the same changes as occur in the native viral gp120-gp41 oligomer. The detailed characterization of the 803-15.6 epitope may be useful for further study of the role of the C5 region of gp120 in the viral attachment and fusion process.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Animal Antigens, CD4/METABOLISM Binding Sites Circular Dichroism Conserved Sequence Epitope Mapping Epitopes/*CHEMISTRY/METABOLISM Female HIV Envelope Protein gp120/*CHEMISTRY/METABOLISM HIV-1/*CHEMISTRY Mice Mice, Inbred BALB C Molecular Sequence Data Protein Conformation Recombinant Proteins/CHEMISTRY/METABOLISM Structure-Activity Relationship Support, Non-U.S. Gov't Surface Plasmon Resonance
991230
A99C0999

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