Conserved structural elements in the V3 crown of HIV-1 gp120

• Published in: Nature structural & molecular biology Vol. 17; no. 8; pp. 955 - 961
• Main Authors: Jiang, Xunqing, Burke, Valicia, Totrov, Maxim, Williams, Constance, Cardozo, Timothy, Gorny, Miroslaw K, Zolla-Pazner, Susan, Kong, Xiang-Peng
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2010; Nature Publishing Group
• Subjects: 60 APPLIED LIFE SCIENCES; 631/250/2152/2153/1291; 631/326/596/1787; 631/326/596/2148; 631/45/535; AIDS vaccines; AIDS VIRUS; Amino Acid Sequence; Analysis; ANTIBODIES; Antibodies, Monoclonal - immunology; Antibody Specificity - immunology; Antigenic determinants; BASIC BIOLOGICAL SCIENCES; Binding; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; CC chemokine receptors; Cellular biology; Conserved Sequence; Crystallography, X-Ray; CXCR4 protein; DESIGN; Epitopes; Epitopes - immunology; Genetic aspects; Glycoprotein gp120; GLYCOPROTEINS; HIV; HIV (Viruses); HIV Envelope Protein gp120 - chemistry; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Immunoglobulin Fragments - chemistry; Life Sciences; Membrane Biology; Models, Molecular; Molecular biology; Molecular Sequence Data; MONOCLONAL ANTIBODIES; national synchrotron light source; Neutralizing; PEPTIDES; Peptides - chemistry; Physiological aspects; Protein Structure; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Alignment; Species Specificity; Structural analysis; Structural members; VACCINES; Variable region; United States
• ISSN: 1545-9993; 1545-9985; 1545-9985
• DOI: 10.1038/nsmb.1861

The V3 crown region of HIV-1 gp120 is involved in binding to co-receptors CCR5 and CXCR4, and show high sequence variability. Structural work with cross-clade neutralizing antibodies in complex with V3 peptides now reveals conserved structural elements in this variable region, which are minimally affected by sequence variation. Binding of the third variable region (V3) of the HIV-1 envelope glycoprotein gp120 to the cell-surface coreceptors CCR5 or CXCR4 during viral entry suggests that there are conserved structural elements in this sequence-variable region. These conserved elements could serve as epitopes to be targeted by a vaccine against HIV-1. Here we perform a systematic structural analysis of representative human anti-V3 monoclonal antibodies in complex with V3 peptides, revealing that the crown of V3 has four conserved structural elements: an arch, a band, a hydrophobic core and the peptide backbone. These are either unaffected by or are subject to minimal sequence variation. As these regions are targeted by cross-clade neutralizing human antibodies, they provide a blueprint for the design of vaccine immunogens that could elicit broadly cross-reactive protective antibodies.