Wyatt R, Kwong P, Desjardins E, Sweet R, Robinson J, Hendrickson W, Sodroski J; Keystone Symposia on Molecular and Cellular Biology: 1998 HIV Pathogenesis and Treatment.
Keyst Symp Mol Cell Biol Keyst Symp Mol Cell Biol.
1998 Mar 13-19; 105 (abstract no. 4098).
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA.
The HIV-1 envelope glycoproteins mediate entry of the virus into CD4-positive target cells. The HIV-1 exterior envelope glycoprotein, gp120, consists of five variable regions interposed among more conserved regions. HIV-1 gp120 mediates attachment to both the primary receptor, CD4, as well as to specific co-receptor molecules from the chemokine receptor family. Due to its exposed location on the viral surface, gp120 is the major target for neutralizing antibodies. Knowledge of gp120 structure at the atomic level of resolution is crucial to elucidate the features of gp120 regions recognized by neutralizing antibodies, as well as to define specific gp120-receptor contacts that may be targets for antiviral drug design. Recently we have crystallized a gp120 core protein in a ternary complex with CD4 and a neutralizing antibody. The structural solution at 2.5Angstrom resolution of the gp120 core reveals 5 alpha-helices and 25 beta-strands arranged into two distinct domains. The outer domain possesses a highly variable face and many N-linked carbohydrate attachment sites. The inner domain contains a conserved inner surface implicated in trimer contacts. Receptor binding is mediated by moieties from both domains. The gp120 core possesses a recessed CD4 binding site that makes extensive contacts with the first domain of CD4. Broadly neutralizing antibodies access the conserved CD4 binding site canyon or conserved elements of the chemokine receptor-binding site. These data will be used to derive a trimeric model of gp120 oligomeric structure.
- Antigens, CD4
- Binding Sites
- HIV Envelope Protein gp120
- Protein Binding
From Meeting Abstracts