NMR-derived solution conformations of a hybrid synthetic peptide containing multiple epitopes of envelope protein gp120 from the RF strain of human immunodeficiency virus.
Solution conformations of a 40-residue hybrid peptide containing T-helper 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 strain RF and contains epitopes that elicit neutralizing antibodies as well as T-cell responses. On the basis of 2D proton NMR spectra (COSY, TOCSY, 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 helical conformation, consistent with a finding that many T-cell antigens 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 V3 region, such as a stretch of beta strand and a kink that may arise from side-chain interactions.
de Lorimier
R
R
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710.
Moody
M A
MA
Haynes
B F
BF
Spicer
L D
LD
D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents; D004220:Disulfides / Q000737:chemistry; D000939:Epitopes / Q000737:chemistry*; D006678:HIV / Q000737:chemistry* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D003432:Cross-Linking Reagents; D004220:Disulfides; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011993:Recombinant Fusion Proteins