Solid-state NMR evidence for an antibody-dependent conformation of the V3 loop of HIV-1 gp120

Solid-state NMR measurements have been carried out on frozen solutions of t he complex of a 24-residue peptide derived from the third variable (V3)\ lo op of the HIV-1 envelope glycoprotein gp120 bound to the lab fragment of an anti-gp120 antibody. The measurements place strong constraints on the conf ormation of the conserved central GPGR motif of the V3 loop in the antibody -bound state. In combination with earlier crystal structures of V3 peptide- antibody complexes and existing data on the cross-reactivity of the antibod ies, the solid-state NMR measurements suggest that the Gly-Pro-Gly-Arg (GPG R) motif adopts an antibody-dependent conformation in the bound state and m ay be conformationally heterogeneous in unbound, full-length gp120, These m easurements are the first application of solid-state NMR methods in a struc tural study of a peptide-protein complex.