Redefining cholesterol's role in the mechanism of the cholesterol's-dependent cytolysins

被引:152
作者
Giddings, KS
Johnson, AE
Tweten, RK
机构
[1] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA
[2] Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Biochem & Genet, College Stn, TX 77843 USA
[3] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA
[4] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA
关键词
D O I
10.1073/pnas.2033520100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The cholesterol-dependent cytolysins (CDCs) constitute a large family of pore-forming toxins that function exclusively on cholesterol -containing membranes. A detailed analysis of the various stages in the cytolytic mechanism of three members of the CDC family revealed that significant depletion of cholesterol from the erythrocyte membrane stalls these toxins in the prepore complex. Therefore, the depletion of membrane cholesterol prevents the insertion of the transmembrane beta-barrel and pore formation. These unprecedented findings provide a paradigm for the involvement: of cholesterol in the CDC cytolytic mechanism and that of other pore-forming toxins whose activity is enhanced by the presence of membrane cholesterol.
引用
收藏
页码:11315 / 11320
页数:6
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