Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
Characterization of simian immunodeficiency virus fusion peptide.
Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:31 (abstract no. 15). Unique Identifier : AIDSLINE PRIM8/900015 Lambrecht B; Brasseur R; Bex F; Burny A; Horth M; Department of Molecular Biology, University of Brussels, 67 rue; des Chevaux, 1640 Rhode-St-Gen/gese, Belgium
Abstract:
The aim of our work is the study of the fusogenic domain of SIV glycoproteins: this highly hydrophobic region is located just after the cleavage site at the amino-terminus of the transmembrane glycoprotein. The tridimensional conformation in a lipid bilayer, of fusion peptides of 30 syncytia-inducing viruses including SIV, arranged as alpha helixes, has been theoritically investigated: all adopt an asymmetric distribution of hydrophobicity along the alpha helix axis leading to oblique insertion in the lipid bilayer. This unusual oblique orientation was proposed to locally disorganize of the lipid bilayer, and to induce membrane fusion. To test this hypothesis, the SIV fusion peptide has been modified by site-directed mutagenesis in such a way to mainly preserve global hydrophobicity but to modify the theoritical tilt of insertion relatively to the water-lipid interface in the lipid bilayer. The fusogenic properties of the mutated glycoproteins have been tested after infection of T4 lymphocytes by a recombinant vaccinia virus. Mutations that modify the angle of insertion lead to a reduced fusogenic potential. On contrast,. mutations that conserve the oblique orientation, do not alter fusogenic properties. These results support the importance of obliquity of insertion in fusion activity.
Keywords: Animal CD4-Positive T-Lymphocytes/METABOLISM Glycoproteins/CHEMISTRY/*GENETICS Lipid Bilayers/CHEMISTRY Mutagenesis, Site-Directed Protein Conformation Recombinant Proteins/BIOSYNTHESIS Solubility SIV/*GENETICS Vaccinia Virus/PHYSIOLOGY ABSTRACT 910730
M9170979
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