重新定义胆固醇在胆固醇依赖性细胞溶素作用机制中的作用。
Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins.
作者信息
Giddings Kara S, Johnson Arthur E, Tweten Rodney K
机构信息
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
出版信息
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11315-20. doi: 10.1073/pnas.2033520100. Epub 2003 Sep 19.
Abstract
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.
摘要
胆固醇依赖细胞溶素（CDCs）构成了一类大型的成孔毒素家族，它们仅在含胆固醇的膜上发挥作用。对CDC家族三个成员细胞溶解机制不同阶段的详细分析表明，红细胞膜中胆固醇的显著消耗会使这些毒素在孔前复合物中停滞。因此，膜胆固醇的消耗会阻止跨膜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细胞溶解机制以及其他因膜胆固醇的存在而增强活性的成孔毒素的机制提供了一个范例。
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