Perfringolysin O structure and mechanism of pore formation as a paradigm for cholesterol-dependent cytolysins.

Perfringolysin O structure and mechanism of pore formation as a paradigm for cholesterol-dependent cytolysins.
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DOI:
10.1007/978-94-017-8881-6_5
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发表时间:
2014
影响因子:
--
通讯作者:
Heuck AP
Heuck AP
中科院分区:
其他
文献类型:
--
作者:
Johnson BB;Heuck AP

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胆固醇依赖性细胞溶素(cdc)是革兰氏阳性菌分泌的一类成孔毒素。这些毒素通过在含胆固醇的膜双层中插入一个大的β桶形成跨膜孔。水溶性cdc与膜的结合触发了含有35-50个单体的低聚物的形成。将70多个β发夹协调地插入膜中需要多次结构构象变化。由产气荚膜梭菌分泌的气溶素O (PFO)已成为cdc的原型。在本章中,我们将描述目前关于PFO细胞溶解机制的知识,特别关注胆固醇识别、寡聚化和涉及孔形成的构象变化。
Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram positive bacteria. These toxins form transmembrane pores by inserting a large β-barrel into cholesterol-containing membrane bilayers. Binding of water-soluble CDCs to the membrane triggers the formation of oligomers containing 35-50 monomers. The coordinated insertion of more than seventy β-hairpins into the membrane requires multiple structural conformational changes. Perfringolysin O (PFO), secreted by Clostridium perfringens, has become the prototype for the CDCs. In this chapter, we will describe current knowledge on the mechanism of PFO cytolysis, with special focus on cholesterol recognition, oligomerization, and the conformational changes involved in pore formation.