The influenza fusion peptide adopts a flexible flat V conformation in membranes.
Knowledge about the influenza fusion peptide (FP) membrane insertion mode is crucial for understanding its fusogenic mechanism. NMR and electron paramagnetic resonance experiments showed that in micelles, the FP inserted as a fixed-angle inverted V. In membranes, however, it was shown to insert as a straight α-helix (by molecular-dynamics simulations) and to adopt multiple kinked conformations (by solid-state NMR). In this work we performed explicit-solvent molecular-dynamics simulations of the influenza FP, and its F9A and W14A mutants, in POPC membranes. The Hα1 chemical shifts predicted from the molecular-dynamics structures are in excellent agreement with the experimental values obtained for the three peptides. The peptide orientation and conformations observed from the simulations lead to a flexible flat-V model in which the peptide lies almost flat on the membrane surface and alternates between kinked and straight-helix conformations.
Département de Biochimie, Microbiologie et Bio-informatique, Institut de Biologie Intégrative et des Systèmes, and Centre de Recherche sur la Fonction, la Structure et l'Ingénierie des Protéines, Université Laval, Quebec City, Quebec, Canada.
Sébastien
S
Légaré
Patrick
P
Lagüe
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D018583:Pliability; D017433:Protein Structure, Secondary; D013997:Time Factors; D053586:Virus Internalization
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D050505:Mutant Proteins; D010455:Peptides; D010710:Phosphates