Redefining cholesterol's role in the mechanism of the cholesterol's-dependent cytolysins
Redefining cholesterol's role in the mechanism of the cholesterol's-dependent cytolysins
复制标题
DOI：
10.1073/pnas.2033520100
复制
发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Tweten, RK
中科院分区：
文献类型：
--
作者：
Giddings, KS;Johnson, AE;Tweten, RK
胆固醇依赖性细胞溶素（CDCs）是一大类成孔毒素，仅在含胆固醇的细胞膜上起作用。对三个CDC家族成员的细胞溶解机制的各个阶段的详细分析表明，红细胞膜上胆固醇的显著消耗阻止了这些毒素在prepore复合物中的存在。因此，膜胆固醇的消耗阻止了跨膜β -桶的插入和孔的形成。这些前所未有的发现为胆固醇参与CDC细胞溶解机制和其他成孔毒素（其活性因膜胆固醇的存在而增强）提供了范例。
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.