Mode of insertion into a lipid membrane of the N-terminal HIV gp41 peptide segment.

Abstract

The complete amino-acid sequence of the gp160 polyprotein of HIV (strain WMJ1) has been analyzed by the Eisenberg procedure. The region surrounding the cleavage site between the gp120 and the gp41 subunit contains a receptor-like region immediately followed by a transmembrane-like region containing approximately 13 residues. These two regions are separated by the cleavage site between gp120 and gp41. Since the same arrangement exists in some paramyxoviruses (unpublished observation) and since the effective cleavage between a receptor-like region and the transmembrane-like region is required in paramyxoviruses to generate fusogenic segment (located at the N-terminal sequence of the transmembrane-like region), we have focused our analysis on the conformational properties of the N-terminal peptide segment of HIV gp41. This peptide segment, which consists of a helical structure according to Garnier prediction, was oriented at the lipid-water interface using a theoretical analysis method that we recently developed. Analysis of the transmembrane peptide determined by Eisenberg method shows that the helical segment orients itself in the lipid monolayer obliquely with respect to the lipid-water interface. Since this rather unusual orientation for a membrane segment of a protein is also found in the fusogenic peptide of the Newcastle Disease Virus (Virus Genes, in press) and seems to possess membrane destabilizing properties, it is in agreement with previous reports suggesting a fusogenic role for the N-terminal part of gp41.