Cholesterol-dependent cytolysins(CDC)are pore forming toxins.A prototype of the CDC family members is perfringolysin O(PFO),which directly binds to the cell membrane enriched in cholesterol,causing cell lysis.However,...Cholesterol-dependent cytolysins(CDC)are pore forming toxins.A prototype of the CDC family members is perfringolysin O(PFO),which directly binds to the cell membrane enriched in cholesterol,causing cell lysis.However,an exception of this general observation is intermedilysin(ILY)of Streptococcus intermedius,which requires human CD59 as a receptor in addition to cholesterol for its hemolytic activity.A possible explanation of this functional difference is the conformational variation between the C-terminal domains of the two toxins,particularly in the highly conserved undecapeptide termed tryptophan rich motif.Here,we present the crystal structure of suilysin,a CDC toxin from the infectious swine pathogen Streptococcus suis.Like PFO,suilysin does not require a host receptor for hemolytic activity;yet the crystal structure of suilysin exhibits a similar conformation in the tryptophan rich motif to ILY.This observation suggests that the current view of the structure-function relationship between CDC proteins and membrane association is far from complete.展开更多
Trichosanthin （TCS） is a plant toxin with ribosome-inactivating activity. TCS can be internalized by the host cells and then attacks the ribosomes resulting in cell death. However, the manner for endocytic uptake of...Trichosanthin （TCS） is a plant toxin with ribosome-inactivating activity. TCS can be internalized by the host cells and then attacks the ribosomes resulting in cell death. However, the manner for endocytic uptake of TCS is not well understood. The present work investigates the endocytosis pathway of TCS in human choriocarcinoma cells. The different endocytic mechanisms are interfered by potassium depletion, cholesterol-extraction/addition, or treatments of various drugs. The experiments detect their effects on the TCS-uptake. The results show that a large portion of the TCS can be internalized by clathrin-dependent, as well as by clathrin-independent but cholesterol-dependent endocytosis in human choriocarcinoma cells.展开更多
基金This work was supported by the National Programs for High Technology Research and Development Program(863 Program)No.2006AA02A322to X.L.,the CAS grant KSCX2-YW-05 to Z.R,the Project of Protein Studies(CAS)grant 2006CB10903National Basic Research Program(973 Program)No.2007CB914304.
文摘Cholesterol-dependent cytolysins(CDC)are pore forming toxins.A prototype of the CDC family members is perfringolysin O(PFO),which directly binds to the cell membrane enriched in cholesterol,causing cell lysis.However,an exception of this general observation is intermedilysin(ILY)of Streptococcus intermedius,which requires human CD59 as a receptor in addition to cholesterol for its hemolytic activity.A possible explanation of this functional difference is the conformational variation between the C-terminal domains of the two toxins,particularly in the highly conserved undecapeptide termed tryptophan rich motif.Here,we present the crystal structure of suilysin,a CDC toxin from the infectious swine pathogen Streptococcus suis.Like PFO,suilysin does not require a host receptor for hemolytic activity;yet the crystal structure of suilysin exhibits a similar conformation in the tryptophan rich motif to ILY.This observation suggests that the current view of the structure-function relationship between CDC proteins and membrane association is far from complete.
基金Supported by the National Key Basic Research and Development (973) Program of China (No. 2004CB20005)
文摘Trichosanthin （TCS） is a plant toxin with ribosome-inactivating activity. TCS can be internalized by the host cells and then attacks the ribosomes resulting in cell death. However, the manner for endocytic uptake of TCS is not well understood. The present work investigates the endocytosis pathway of TCS in human choriocarcinoma cells. The different endocytic mechanisms are interfered by potassium depletion, cholesterol-extraction/addition, or treatments of various drugs. The experiments detect their effects on the TCS-uptake. The results show that a large portion of the TCS can be internalized by clathrin-dependent, as well as by clathrin-independent but cholesterol-dependent endocytosis in human choriocarcinoma cells.
