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 the complex of a 24-residue peptide derived from the third variable (V3) loop of the HIV-1 envelope glycoprotein gp120 bound to the Fab fragment of an anti-gp120 antibody. The measurements place strong constraints on the conformation 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 antibodies, the solid-state NMR measurements suggest that the Gly-Pro-Gly-Arg (GPGR) motif adopts an antibody-dependent conformation in the bound state and may be conformationally heterogeneous in unbound, full-length gp120. These measurements are the first application of solid-state NMR methods in a structural study of a peptide-protein complex.
Department of Chemistry, Michigan State University, East Lansing 48824, USA.
D P
DP
Weliky
A E
AE
Bennett
A
A
Zvi
J
J
Anglister
P J
PJ
Steinbach
R
R
Tycko
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation
D000906:Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments