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 β hairpin. This structure of V3_MN was found to have conformation and sequence similarities to β hairpins in CD8 and CCR5 ligands MIP-1α, MIP-1β, and RANTES and differed from the β hairpin of a V3_IIIB peptide bound to the strain-specific murine anti-gp120_IIIB antibody 0.5β. In contrast to the structure of the bound V3_MN peptide, the V3_IIIB peptide resembles a β hairpin in SDF-1, a CXCR4 ligand. These data suggest that the 447-52D-bound V3_MN and the 0.5β-bound V3_IIIB structures represent alternative V3 conformations responsible for selective interactions with CCR5 and CXCR4, respectively.