Solution conformation of an immunogenic peptide derived from the principal neutralizing determinant of the HIV-2 envelope glycoprotein gp125.
BACKGROUND
The conformational preferences of a number of peptides with sequences related to the envelope glycoproteins of HIV-1 have been investigated in the past few years. Similar studies have not been made for HIV-2, which is a distinct virus with similar physiological effects to those of HIV-1. The discovery of common structural features would be a promising route to the design of immunogens for generally effective HIV vaccines. We present the results of an NMR conformational study of a sequence deriving from the V3 loop of HIV-2.


RESULTS
Three synthetic immunogenic peptides were studied, of 12, 22 and 39 amino acids in length, all containing a central Met-Ser-Gly-Arg sequence conserved among a number of HIV-2 isolates. In addition, the 39-mer contained a disulfide bond between cysteine residues close to the ends of the molecule, forming a loop that is thought to comprise an important structural and immunological component of the intact glycoprotein. All three peptides display well defined beta-turns in the Met-Ser-Gly-Arg sequence, independent of the integrity of the disulfide bond. No other conformational preferences for folded conformations were found for the peptides.


CONCLUSIONS
The presence of a beta-turn in the Met-Ser-Gly-Arg sequence is strikingly similar to the behavior seen for the corresponding principal neutralizing determinant sequence from gp120 of HIV-1 and argues, in the absence of information of the three-dimensional structure of the intact proteins, for a similarity in the structure of this region that could be exploited in the design of synthetic peptide vaccines generally effective against HIV infections.
Campbell
A P
AP
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Sykes
B D
BD
Norrby
E
E
Assa-Munt
N
N
Dyson
H J
HJ
D016915:AIDS Vaccines / Q000737:chemistry; D000595:Amino Acid Sequence; D004220:Disulfides / Q000737:chemistry; D015195:Drug Design; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D015488:HIV Antigens / Q000737:chemistry* / Q000235:genetics; D015498:HIV-2 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009500:Neutralization Tests; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D014614:Vaccines, Synthetic / Q000737:chemistry; D054299:env Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D004220:Disulfides; D015686:Gene Products, env; D015488:HIV Antigens; D010455:Peptides; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C066316:gp125 envelope protein, Human immunodeficiency virus 2