Alternative conformations of HIV-1 V3 loops mimic beta hairpins in chemokines, suggesting a mechanism for coreceptor selectivity.
The V3 loop of the HIV-1 envelope glycoprotein gp120 is involved in binding to the CCR5 and CXCR4 coreceptors. The structure of an HIV-1(MN) V3 peptide bound to the Fv of the broadly neutralizing human monoclonal antibody 447-52D was solved by NMR and found to be a beta hairpin. This structure of V3(MN) was found to have conformation and sequence similarities to beta hairpins in CD8 and CCR5 ligands MIP-1alpha, MIP-1beta, and RANTES and differed from the beta hairpin of a V3(IIIB) peptide bound to the strain-specific murine anti-gp120(IIIB) antibody 0.5beta. In contrast to the structure of the bound V3(MN) peptide, the V3(IIIB) peptide resembles a beta hairpin in SDF-1, a CXCR4 ligand. These data suggest that the 447-52D-bound V3(MN) and the 0.5beta-bound V3(IIIB) structures represent alternative V3 conformations responsible for selective interactions with CCR5 and CXCR4, respectively.
Sharon
Michal
M
Department of Structural Biology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Kessler
Naama
N
Levy
Rina
R
Zolla-Pazner
Susan
S
Görlach
Matthias
M
Anglister
Jacob
J
D000906:Antibodies / Q000276:immunology; D018925:Chemokines / Q000737:chemistry*; D000939:Epitopes; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000906:Antibodies; D018925:Chemokines; D000939:Epitopes; D015699:HIV Envelope Protein gp120