Solid−state NMR evidence for an antibody−dependent conformation
of the V3 loop of HIV−1 gp120
David P. Weliky1, 2, Andrew E. Bennett2, Anat Zvi3, Jacob Anglister3, Peter J. Steinbach4
& Robert Tycko2
1
Department of Chemistry, Michigan State University,
East Lansing, Michigan 48824, USA.
2
Laboratory of Chemical Physics, National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,
Bethesda, Maryland 20892-0520, USA
3
Department of Structural Biology, The Weizmann Institute
of Science, Rehovot 76100, Israel.
4
Center for Molecular Modeling, Center for Information
Technology, National Insitutes of Health, Bethesda,
Maryland 20892-5626, USA.
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.
