NMR studies of V3 peptide complexes with antibodies suggest a mechanism for HIV-1 co-receptor selectivity.
The third variable region (V3) of the HIV-1 envelope glycoprotein gp120 is involved in gp120 binding to the chemokine receptors CCR5 and CXCR4, which serve as co-receptors in HIV-1 infection. The sequence of V3 determines whether the virus binds to CCR5 and infects predominantly macrophages (R5 virus) or to CXCR4 and infects mostly T-cells (X4 virus). This review summarizes structural information for V3 peptides in complex with HIV-1 neutralizing antibodies. Nuclear magnetic resonance studies of the V3 peptides led to the proposal of a mechanism for co-receptor selectivity. Experiments to further explore this mechanism and potential applications of V3 structural information are discussed.
Sharon
Michal
M
Weizmann Institute of Science, Department of Structural Biology, Rehovot 76100, Israel.
Rosen
Osnat
O
Anglister
Jacob
J
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D019707:Receptors, Chemokine / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019707:Receptors, Chemokine