title: Biophysical characterization and membrane interaction of the most membranotropic region of the HIV-1 gp41 endodomain.
abstract: The membrane fusion protein of HIV-1 is the envelope transmembrane gp41 glycoprotein, which is the responsible of the membrane fusion between the virus and the target cell. Gp41 has an unusual cytoplasmic tail, the endodomain, containing highly helicoidal segments with large hydrophobic moments, the so called lentivirus lytic peptides or LLPs. According to our previous work, one of the most membranotropic regions along the whole gp41 glycoprotein was located in the LLP3 region of the gp41. In order to get new insights into the viral membrane fusion mechanism, a peptide pertaining to the LLP3 domain has been studied by infrared, fluorescence and calorimetry regarding its structure, its ability to induce membrane rupture and aggregation, as well as its affinity towards specific phospholipids. Our results demonstrate that this peptide interacts with phospholipid-containing model membranes, affects the phase-behavior of membrane phospholipids and induces leakage and aggregation of liposomes. The membrane-perturbing properties of LLP3, together with the possibility that the Kennedy sequence could be part of an external loop, open the possibility that these domains might function in modulating viral membrane fusion or budding, synergistically with other membranotropic regions of the gp41 glycoprotein.
authors.affiliation: Instituto de Biología Molecular y Celular, Edf. Torregaitán, Campus de Elche, Universidad Miguel Hernández, E-03202 Elche-Alicante, Spain.
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Moreno
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Pérez-Berná
authors.forename: Jaime
authors.initials: J
authors.lastname: Guillén
authors.forename: José
authors.initials: J
authors.lastname: Villalaín
mesh_terms: D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D002152:Calorimetry, Differential Scanning; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D015700:HIV Envelope Protein gp41