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 (a helix or β 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 β and helical + unordered structures in aqueous buffer. Model membranes are shown to enhance the formation of aggregated β 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 β structures upon binding to the membrane. © 2005 American Chemical Society.
|Publication status||Published - 11 Oct 2005|