NMR-DERIVED SOLUTION CONFORMATIONS OF A HYBRID SYNTHETIC PEPTIDE-CONTAINING MULTIPLE EPITOPES OF ENVELOPE PROTEIN GP120 FROM THE RF STRAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS
R. Delorimier et al., NMR-DERIVED SOLUTION CONFORMATIONS OF A HYBRID SYNTHETIC PEPTIDE-CONTAINING MULTIPLE EPITOPES OF ENVELOPE PROTEIN GP120 FROM THE RF STRAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS, Biochemistry, 33(8), 1994, pp. 2055-2062
Solution conformations of a 40-residue hybrid peptide containing T-hel
per epitopes and B-cell determinants from envelope glycoprotein gp120
of human immunodeficiency virus (HIV) have been investigated with NMR.
Peptides of this general design are highly immunogenic and induce HIV
-neutralizing antibodies and T-lymphocyte responses. The 16-residue N-
terminal segment of the peptide contains a T-helper epitope, while the
24-residue C-terminal segment is derived from the V3 loop of HIV stra
in RF and contains epitopes that elicit neutralizing antibodies as wel
l as T-cell responses. On the basis of 2D proton NMR spectra (COSY, TO
CSY, and NOESY) of the peptide in aqueous solution, the resonances of
nearly all hydrogens are assigned. The peptide is largely disordered,
but specific medium-range NOEs demonstrate conformational preferences
in certain regions. Part of the N-terminal segment exhibits nascent he
lical conformations, consistent with a finding that many T-cell antige
ns can be modeled as amphipathic helices. In the V3-derived segment of
the peptide, one region shows evidence of a tight turn conformation,
corresponding to a turn found previously in V3 peptides of HIV strains
MN and IIIB. Other conformational features are also detected in the V
3 region, such as a stretch of beta strand and a kink that may arise f
rom side-chain interactions.