Biophysical characterization of the structure of the amino-terminal regionof gp41 of HIV-1 - Implications on viral fusion mechanism

A peptide of 51 amino acids corresponding to the NH2-terminal region (5-55) of the glycoprotein gp41 of human immunodeficiency virus type 1 was synthe sized to study its conformation and assembly. Nuclear magnetic resonance ex periments indicated the sequence NH2-terminal to the leucine zipper-like do main of gp41 was induced into helix in the micellar solution, in agreement with circular dichroism data. Light scattering experiment showed that the p eptide molecules self-assembled in water into trimeric structure on average . That the peptide molecules oligomerize in aqueous solution was supported by gel filtration and diffusion coefficient experiments. Molecular dynamics simulation based on the NMR data revealed a flexible region adjacent to th e hydrophobic NH2, terminus of gp41. The biological significance of the pre sent findings on the conformational flexibility and the propensity of oligo merization of the peptide may be envisioned by a proposed model for the int eraction of gp41 with membranes during fusion process.