Selective destabilization of acidic phospholipid bilayers performed by thehepatitis B virus fusion peptide

A peptide corresponding to the N-terminal region of the S protein of hepati tis B virus (Met-Glu-Asn-Ile-Thr-Ser-Gly-PheLeu-Gly-Pro-Leu-Leu-Val-Leu-Gln ) has been previously demonstrated to perform aggregation and destabilizati on of acidic liposome bilayers and to adopt a highly stable P-sheet conform ation in the presence of phospholipids. The changes in the lipid moiety pro duced by this peptide have been followed by fluorescence depolarization and electron microscopy, The later was employed to determine the size and shap e of the peptide-vesicle complexes, showing the presence of highly aggregat ed and fused structures only when negatively charged liposomes were employe d. 1,6-Diphenyl-1,3,5-hexatriene depolarization measurements showed that th e interaction of the peptide with both negatively charged and zwitterionic liposomes was accompanied by a substantial reduction of the transition ampl itude without affecting the temperature of the gel-to-liquid crystalline ph ase transition. These data are indicative of the peptide insertion inside t he bilayer of both types of liposomes affecting the acyl chain order, thoug h only the interaction with acidic phospholipids leads to aggregation and f usion, This preferential destabilization of the peptide towards negatively charged phospholipids can be ascribed to the electrostatic interactions bet ween the peptide and the polar head groups, as monitored by 1-(4-(trimethyl ammoniumphenyl)-6-phenyl-1,3,5-hexatriene fluorescence depolarization analy sis. (C) 2000 Elsevier Science B.V. All rights reserved.