title: Interaction of fusion peptides from HIV gp41 with membranes: a time-resolved membrane binding, lipid mixing, and structural study.
abstract: The interaction of the so-called fusion peptide of the human immunodeficiency virus gp41 envelope glycoprotein with the target cell membrane is believed to trigger the fusion process which allows the entry of the virus into the cell. Many studies on the interaction of the fusion peptide with biological membranes have been carried out using synthetic peptides and model membranes. Due to the variety of experimental systems and sequences used, some controversy exists, concerning mainly the type of structure which triggers membrane destabilization and fusion (alpha helix or beta structure). With the aim of contributing to shed some light on the subject we have undertaken a series of experiments on the interaction of the three most representative fusion sequences with model membranes under the same experimental conditions. The results show that the fusion peptides, which adopt an unordered structure when dissolved in DMSO, form a mixture of aggregated beta and helical + unordered structures in aqueous buffer. Model membranes are shown to enhance the formation of aggregated beta structures. The nature of the membrane binding event, the kinetics of the binding and lipid mixing processes, and the kinetics of the structural changes depend on whether both ends of the fusion sequence or just one bears a positive charge. Analysis of the kinetic data shows that lipid mixing depends on the transformation of unordered + helical structures into aggregated beta structures upon binding to the membrane.
authors.affiliation: Unitat de Biofísica, Departament de Bioquímica i de Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Buzón
authors.forename: Esteve
authors.initials: E
authors.lastname: Padrós
authors.forename: Josep
authors.initials: J
authors.lastname: Cladera
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015497:HIV-1 / Q000378:metabolism*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D015700:HIV Envelope Protein gp41; D008055:Lipids; D010455:Peptides; D004121:Dimethyl Sulfoxide