Structure of a V3-Containing HIV-1 gp120 Core

• Published in: Science (American Association for the Advancement of Science) Vol. 310; no. 5750; pp. 1025 - 1028
• Main Authors: Huang, Chih-chin, Tang, Min, Zhang, Mei-Yun, Majeed, Shahzad, Montabana, Elizabeth, Stanfield, Robyn L, Dimitrov, Dimiter S, Korber, Bette, Sodroski, Joseph, Wilson, Ian A, Wyatt, Richard, Kwong, Peter D
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 11-11-2005; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Analysis; Antibodies; Atoms; Binding Sites; Biological and medical sciences; CD4 Antigens - chemistry; CD4 Antigens - metabolism; Cell membranes; Crystallization; Crystallography, X-Ray; Fundamental and applied biological sciences. Psychology; Glycoproteins; HIV; HIV (Viruses); HIV 1; HIV Antibodies - immunology; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV-1 - chemistry; HIV-1 - immunology; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hydrogen Bonding; Immunodominant Epitopes; Immunology; Microbiology; Models, Molecular; Molecular Sequence Data; Molecular structure; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptide Fragments - metabolism; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Receptors; Receptors, CCR5 - chemistry; Receptors, CCR5 - metabolism; Receptors, CXCR4 - chemistry; Receptors, CXCR4 - metabolism; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Research facilities; Structural Analysis (Linguistics); Structural Analysis (Science); Trimers; Virology; Viruses; Virus; HIV-1 virus; Antibody; Variable region; Glycoprotein; Retroviridae; Human immunodeficiency virus; Target cell; Immunodominance; Lentivirus; Cell surface; Neutralization
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1118398

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.