胆固醇依赖型细胞裂解素的成“孔”机制简述

Introduction about The Hemolysis Mechanism of Cholesterol-Dependent Cytolysins

胆固醇依赖型细胞裂解素(Cholesterol-dependent cytolysins,简称CDC)是革兰氏阳性菌在感染宿主时分泌的一种重要的毒力因子。CDC的一个特性就是可以在富含胆固醇的细胞膜上寡聚成"孔"。此寡聚的发生机理及其结构基础在过去15年中为人们高度重视,相关研究发表在"Cell"、"Science"等杂志上。代表性成果包括四个CDC的高分辨率晶体结构、CDC单体寡聚所成的"孔"的电镜结构等。目前,虽然CDC成"孔"过程的细节还没有被完全阐明,但是关于此过程几个要点的假设已经被普遍接受:胆固醇介导结构域4(位于蛋白的C端)的三个疏水环与膜相互作用;结构域3是穿膜结构域,成"孔"过程中,此结构域的6个α螺旋转变成β折叠穿膜。该文将围绕上述内容并结合目前最新的研究成果对CDC成"孔"机制作一介绍。

Cholesterol-dependent cytolysins are considered as important virulence factors in the pathogenesis of Gram-positive bacteria infection.Members of CDC family are secreted as water soluble monomer and able to oligomerize on membrane surface with the assistance of cholesterol / cholesterol and other receptor.The related mechanism was subjected to intensive investigation during the past 15 years.And some of the results were published in ＂Cell＂ and ＂Science＂.So far,although some details of the oligomerization mechanism are still unclear,several hypothesizes are widely accepted such as（1） cholesterol mediates the insertion of three loops（L1-L3） located in domain 4（C-terminal portion of the protein） to the membrane and（2） six α helices in domain 3 transformed into β strands to span the membrane during the pore formation.This mini review will give an introduction on the overall picture of the membrane binding and spanning of CDCs and the remaining questions in the process.