Protein-induced Fusion Can Be Modulated by Target Membrane Lipids through a Structural Switch at the Level of the Fusion Peptide

• Published in: The Journal of biological chemistry 2000-02, Vol.275 (6), p.3936-3942
• Main Authors: Pécheur, Eve-Isabelle, Martin, Isabelle, Bienvenüe, Alain, Ruysschaert, Jean-Marie, Hoekstra, Dick
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry, Molecular Biology; Erythrocytes - metabolism; Golgi Apparatus - metabolism; Influenza virus; Intracellular Membranes - metabolism; Kinetics; Life Sciences; Liposomes - metabolism; Liver - metabolism; Lysophospholipids - pharmacology; Membrane Fusion - drug effects; Membrane Lipids - metabolism; Orthomyxoviridae - metabolism; Peptides - metabolism; Protein Structure, Secondary - drug effects; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.6.3936

Regulatory features of protein-induced membrane fusion are largely unclear, particularly at the level of the fusion peptide. Fusion peptides being part of larger protein complexes, such investigations are met with technical limitations. Here, we show that the fusion activity of influenza virus or Golgi membranes is strongly inhibited by minor amounts of (lyso)lipids when present in the target membrane but not when inserted into the viral or Golgi membrane itself. To investigate the underlying mechanism, we employ a membrane-anchored peptide system and show that fusion is similarly regulated by these lipids when inserted into the target but not when present in the peptide-containing membrane. Peptide-induced fusion is regulated by areversible switch of secondary structure from a fusion-permissive α-helix to a nonfusogenic β-sheet. The “on/off” activation of this switch is governed by minor amounts of (lyso)-phospholipids in targets, causing a drop in α-helix and a dramatic increase in β-sheet contents. Concomitantly, fusion is inhibited, due to impaired peptide insertion into the target membrane. Our observations in biological fusion systems together with the model studies suggest that distinct lipids in target membranes provide a means for regulating membrane fusion by causing a reversible secondary structure switch of the fusion peptides.