title: Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement.
abstract: Cinnamycin is a unique toxin in that its receptor, phosphatidylethanolamine (PE), resides in the inner layer of the plasma membrane. Little is known about how the toxin recognizes PE and causes cytotoxicity. We showed that cinnamycin induced transbilayer phospholipid movement in target cells that leads to the exposure of inner leaflet PE to the toxin. Model membrane studies revealed that cinnamycin induced transbilayer lipid movement in a PE concentration-dependent manner. Re-orientation of phospholipids was accompanied by an increase in the incidence of beta-sheet structure in cinnamycin. When the surface concentration of PE was high, cinnamycin induced membrane re-organization such as membrane fusion and the alteration of membrane gross morphology. These results suggest that cinnamycin promotes its own binding to the cell and causes toxicity by inducing transbilayer lipid movement.
authors.affiliation: Supra-Biomolecular System Research Group, RIKEN Institute of Physical and Chemical Research, Frontier Research System, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Asami
authors.initials: A
authors.lastname: Makino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Baba
authors.forename: Kazushi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Iwamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yano
authors.forename: Nobuo
authors.initials: N
authors.lastname: Terada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohno
authors.forename: Satoshi B
authors.initials: SB
authors.lastname: Sato
authors.forename: Akinori
authors.initials: A
authors.lastname: Ohta
authors.forename: Masato
authors.initials: M
authors.lastname: Umeda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001430:Bacteriocins; D001665:Binding Sites; D019921:Biotinylation; D002470:Cell Survival / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008563:Membrane Lipids / Q000502:physiology*; D010456:Peptides, Cyclic; D010714:Phosphatidylethanolamines / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D010456:Peptides, Cyclic; D010714:Phosphatidylethanolamines; C000485:cinnamycin