Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement.
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.
Makino
Asami
A
Supra-Biomolecular System Research Group, RIKEN Institute of Physical and Chemical Research, Frontier Research System, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Baba
Takeshi
T
Fujimoto
Kazushi
K
Iwamoto
Kunihiko
K
Yano
Yoshiaki
Y
Terada
Nobuo
N
Ohno
Shinichi
S
Sato
Satoshi B
SB
Ohta
Akinori
A
Umeda
Masato
M
Matsuzaki
Katsumi
K
Kobayashi
Toshihide
T
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
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D008051:Lipid Bilayers; D008081:Liposomes; D008563:Membrane Lipids; D010456:Peptides, Cyclic; D010714:Phosphatidylethanolamines; C000485:cinnamycin