title: The structure of a melittin-stabilized pore.
abstract: Melittin has been reported to form toroidal pores under certain conditions, but the atomic-resolution structure of these pores is unknown. A 9-μs all-atom molecular-dynamics simulation starting from a closely packed transmembrane melittin tetramer in DMPC shows formation of a toroidal pore after 1 μs. The pore remains stable with a roughly constant radius for the rest of the simulation. Surprisingly, one or two melittin monomers frequently transition between transmembrane and surface states. All four peptides are largely helical. A simulation in a DMPC/DMPG membrane did not lead to a stable pore, consistent with the experimentally observed lower activity of melittin on anionic membranes. The picture that emerges from this work is rather close to the classical toroidal pore, but more dynamic with respect to the configuration of the peptides.
authors.affiliation: Department of Chemistry, The City College of New York, New York, New York.
authors.forename: John M
authors.initials: JM
authors.lastname: Leveritt
authors.affiliation: Department of Chemistry, The City College of New York, New York, New York.
authors.forename: Almudena
authors.initials: A
authors.lastname: Pino-Angeles
authors.affiliation: Department of Chemistry, The City College of New York, New York, New York. Electronic address: tlazaridis@ccny.cuny.edu.
authors.forename: Themis
authors.initials: T
authors.lastname: Lazaridis
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D055503:Protein Multimerization
chemical_list: D008051:Lipid Bilayers; D008555:Melitten