Mechanism of membrane insertion of a multimeric β-barrel protein:: Perfringolysin O creates a pore using ordered and coupled conformational changes
Mechanism of membrane insertion of a multimeric β-barrel protein:: Perfringolysin O creates a pore using ordered and coupled conformational changes
复制标题
DOI：
10.1016/s1097-2765(00)00119-2
复制
发表时间：
2000-11-01
期刊：
影响因子：
16
通讯作者：
Johnson, AE
中科院分区：
文献类型：
--
作者：
Heuck, AP;Hotze, EM;Johnson, AE
Perfringolysin O 是一种细菌溶细胞毒素，通过将其四个结构域中的两个自发插入双层，在含胆固醇的膜中形成异常大的孔。通过使用荧光光谱监测域特异性构象变化和孔形成的动力学，建立了域-膜相互作用的时间序列。一个膜暴露结构域不会深入渗透到双层中，也不是实际孔的一部分，但负责膜识别。在开始将另一个结构域插入双层之前，该结构域必须与膜结合。尽管两个域在空间上分离，但它们在构象上耦合。因此，溶细胞孔的形成是通过有序构象变化和域间通讯的新机制来完成的。
Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal sequence of domain-membrane interactions has been established. One membrane-exposed domain does not penetrate deeply into the bilayer and is not part of the actual pore, but is responsible for membrane recognition. This domain must bind to the membrane before insertion of the other domain into the bilayer is initiated. The two domains are conformationally coupled, even though they are spatially separated. Thus, cytolytic pore formation is accomplished by a novel mechanism of ordered conformational changes and interdomain communication.