title: Destabilization exerted by peptides derived from the membrane-proximal external region of HIV-1 gp41 in lipid vesicles supporting fluid phase coexistence.
abstract: The human immunodeficiency virus (HIV) envelope is enriched in cholesterol and sphingomyelin, two lipids that sustain the formation of laterally segregated liquid-ordered fluid domains in model systems. Several evidences indicate that the high lipid order existing at the envelope may play a role in HIV pathogenesis. A putative mechanism might involve the modulation of the membrane-perturbing function of the gp41 membrane-proximal external region (MPER). To test such hypothesis, we investigate here the effect of lipid phase coexistence on the membrane-restructuring properties of NpreTM and CpreTM, two peptides based on the amino- and carboxy-terminal MPER sequences, respectively. Fluid phase coexistence elicited the fusogenic activity of NpreTM at high membrane doses and stimulated "graded" leakage at low doses. By comparison, the effect on CpreTM was restricted to an enhancement of "all-or-none" leakage that was consistent with the promotion of its surface aggregation. Confocal microscopy of single vesicles revealed the preference of both peptides for liquid-disordered domains. Accordingly, we speculate that confinement into envelope fluid nanodomains might boost the distinct capacities of HIV MPER hydrophobic modules for inducing membrane defects during fusion.
authors.affiliation: Departamento de Bioquímica, Universidad del País Vasco, 48080 Bilbao, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Apellániz
authors.forename: Ana
authors.initials: A
authors.lastname: García-Sáez
authors.forename: Shlomo
authors.initials: S
authors.lastname: Nir
authors.forename: José L
authors.initials: JL
authors.lastname: Nieva
mesh_terms: D000595:Amino Acid Sequence; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D050356:Lipid Metabolism; D008561:Membrane Fusion; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D015700:HIV Envelope Protein gp41