A monomeric 3(10)-helix is formed in water by a 13-residue peptide representing the neutralizing determinant of HIV-1 on gp41.
The peptide gp41(659-671) (ELLELDKWASLWN) comprises the entire epitope for one of the three known antibodies capable of neutralizing a broad spectrum of primary HIV-1 isolates and is the only such epitope that is sequential. Here we present the NMR structure of gp41(659-671) in water. This peptide forms a monomeric 3(10)-helix stabilized by i,i+3 side chain-side chain interactions favored by its primary sequence. In this conformation the peptide presents an exposed surface, which is mostly hydrophobic and consists of conserved HIV-1 residues. The presence of the 3(10)-helix is confirmed by its characteristic CD pattern. Studies of the 3(10)-helix have been hampered by the absence of a model peptide adopting this conformation. gp41(659-671) can serve as such a model to investigate the spectral characteristics of the 3(10)-helix, the factors that influence its stability, and the propensity of different amino acids to form a 3(10)-helix. The observation that the 3(10)-helical conformation is highly populated in the peptide gp41(659-671) indicates that the corresponding segment in the cognate protein is an autonomous folding unit. As such, it is very likely that the helical conformation is maintained in gp41 throughout the different tertiary structures of the envelope protein that form during the process of viral fusion. However, the exposure of the gp41(659-671) segment may vary, leading to changes in the reactivity of anti-gp41 antibodies in the different stages of viral fusion. Since gp41(659-671) is an autonomous folding unit, peptide immunogens consisting of the complete gp41(659-671) sequence are likely to induce antibodies highly cross-reactive with HIV-1.
Biron
Zohar
Z
Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Khare
Sanjay
S
Samson
Abraham O
AO
Hayek
Yehezkiel
Y
Naider
Fred
F
Anglister
Jacob
J
D000107:Acetylation; D000577:Amides / Q000737:chemistry; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006860:Hydrogen Bonding; D008970:Molecular Weight; D009500:Neutralization Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D013816:Thermodynamics; D014867:Water
D000577:Amides; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012996:Solutions; D014867:Water