Design of a short membrane-destabilizing peptide covalently bound to liposomes.
We characterized the physical and biological properties of a 14-residue amphipathic sequence called SFP (for short fusogenic peptide). At acidic pH, this short synthetic peptide interacts with various phospholipidic monolayers. These interactions were correlated with a pH-dependent conformational transition of SFP resulting in a hydrophobic alpha-helical structure. The hemolysis assay showed a pH-dependent weak membrane destabilizing activity of SFP. However, membrane anchoring of SFP through a covalently bound myristic acid enhanced by 1000-fold its membrane-destabilizing power. Moreover, SFP covalently bound to fluorescent-labeled liposomes induced a pH-dependent mixing of both membranes. SFP, a small synthetic peptide, is thus able to mimick many aspects of viral protein-induced membrane fusion: conformational change, membrane destabilization, membrane anchoring and finally pH-dependent lipid mixing.
Puyal
C
C
URA 530 CNRS Interactions Membranaires, Dépt. Biologie-Santé, Université des Sciences et Techniques du Languedoc, Montpellier, France.
Maurin
L
L
Miquel
G
G
Bienvenüe
A
A
Philippot
J
J
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D017433:Protein Structure, Secondary
D008081:Liposomes; D010455:Peptides; C066951:GALA peptide