gp120: Biologic aspects of structural features.
HIV-1 particles are decorated with a network of densely arranged envelope spikes on their surface. Each spike is formed of a trimer of heterodimers of the gp120 surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1 entry into target cells, initiating the HIV-1 replication cycle. They are a target for entry-blocking drugs and for neutralizing Abs that could contribute to vaccine protection. The crystal structure of the core of gp120 has been recently solved. It reveals the structure of the conserved HIV-1 receptor binding sites and some of the mechanisms evolved by HIV-1 to escape Ab responses. The gp120 consists of three faces. One is largely inaccessible on the native trimer, and two faces are exposed but apparently have low immunogenicity, particularly on primary viruses. We have modeled HIV-1 neutralization by a CD4 binding site monoclonal Ab, and we propose that neutralization takes place by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance. Knowledge of gp120 structure and function should assist in the design of new drugs as well as of an effective vaccine. In the latter case, circumventing the low immunogenicity of the HIV-1 envelope spike is a major challenge.
Poignard
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Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. poignard@scripps.edu
Saphire
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Parren
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Burton
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D016915:AIDS Vaccines; D019380:Anti-HIV Agents / Q000494:pharmacology; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D015195:Drug Design; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D015700:HIV Envelope Protein gp41 / Q000502:physiology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D008958:Models, Molecular; D009500:Neutralization Tests; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000378:metabolism; D013329:Structure-Activity Relationship
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D019713:Receptors, CCR5