Trichosanthin induces leakage and membrane fusion of liposome.
Trichosanthin (TCS) is a ribosome inactivating protein with multiple pharmacological properties. Here the interaction between TCS and a phospholipid bilayer is investigated to provide evidence for membrane translocation mechanism of TCS. The results show that TCS can destabilize liposomes made by phospholipids with negatively charged head group. The destabilization effect is pH-dependent and happens only under acidic conditions. Membrane fusion is also seen to accompany the destabilizing process. The interaction between a phospholipid bilayer and C7, a mutant of TCS with 7 residues at its C-terminus deleted, has been investigated. Deleting the C-terminus almost completely abolishes the destabilizing effect of TCS on the phospholipid bilayer, which implicates the C-terminus in the interaction between trichosanthin and the membrane.
Xia
Xiao-feng
XF
Department of Biological Sciences & Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
Zhang
Fan
F
Shaw
Pang-Chui
PC
Sui
Sen-Fang
SF
D000595:Amino Acid Sequence; D000818:Animals; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008561:Membrane Fusion / Q000187:drug effects*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D012235:Rhodamines; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D015978:Trichosanthin / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*
D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D012235:Rhodamines; D015978:Trichosanthin; D016650:Fluorescein-5-isothiocyanate