A monomeric 3₁₀-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 3₁₀-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 3₁₀-helix is confirmed by its characteristic CD pattern. Studies of the 3₁₀-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 3₁₀-helix, the factors that influence its stability, and the propensity of different amino acids to form a 3₁₀-helix. The observation that the 3₁₀-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.