The SU glycoprotein 120 from HIV-1 penetrates into lipid monolayers mimicking plasma membranes

Increasing evidence suggests that the HN envelope binds through its surface (SU) gp120 not only to receptors and coreceptors, but also to other compon ents of the cellular membrane where the glycolipids appear to be good candi dates. To assess the ability of HIV-1 SU gp120 to penetrate into phospholip id membranes, we carried out a study of the interactions between a recombin ant SU gp120 from HIV-1/HXB2 and artificial lipid monolayers mimicking the composition of the outer leaflet of the lymphocytes and which were spread a t the air-water interface. We show that the protein, in its aggregated form , has amphipathic properties and that the insertion of this amphipathic spe cies into lipids is favored by the presence of sphingomyelin. Furthermore, cholesterol enhances the penetration into mixed phosphatidylcholine-sphingo myelin monolayers, Coexistence of different physical states of the lipids a nd thus of domains appears to play a major role for protein penetration ind ependently of the presence of receptors and coreceptors.