The MACPF/CDC family of pore-forming toxins.

The MACPF/CDC family of pore-forming toxins.
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DOI:
10.1111/j.1462-5822.2008.01191.x
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发表时间:
2008-09
影响因子:
3.4
通讯作者:
Dunstone MA
Dunstone MA
中科院分区:
生物学2区
文献类型:
--
作者:
Rosado CJ;Kondos S;Bull TE;Kuiper MJ;Law RH;Buckle AM;Voskoboinik I;Bird PI;Trapani JA;Whisstock JC;Dunstone MA

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成孔毒素(PFT)通常与细菌致病相关。然而,在真核生物中,PFT在免疫系统中起作用或用于攻击猎物(例如毒液)。本文综述了两个家族的球状蛋白PFT:胆固醇依赖性溶细胞素(CDC)和膜攻击复合物/穿孔素超家族(MACPF)。CDC由革兰氏阳性菌产生,并在感染期间裂解或透化宿主细胞或细胞内细胞器。在真核生物中,MACPF蛋白在免疫、侵袭和发育中具有溶解和非溶解作用。几种CDC的结构和分子机制相对较好地表征。孔形成涉及可溶性单体的低聚和组装成环形预孔,其经历构象变化以插入膜中,形成大的两亲性跨膜β-桶。相比之下,MACPF蛋白的结构和机制仍然不清楚。最近的晶体学研究表明,虽然MACPF和CDC在序列水平上非常不同,但它们有一个共同的折叠。结合生物化学研究,这些结构数据表明,裂解MACPF蛋白质使用CDC样膜破坏机制,并将有助于了解这些蛋白质在免疫和发育中的作用。
Pore-forming toxins (PFTs) are commonly associated with bacterial pathogenesis. In eukaryotes, however, PFTs operate in the immune system or are deployed for attacking prey (e.g. venoms). This review focuses upon two families of globular protein PFTs: the cholesterol-dependent cytolysins (CDCs) and the membrane attack complex/perforin superfamily (MACPF). CDCs are produced by Gram-positive bacteria and lyse or permeabilize host cells or intracellular organelles during infection. In eukaryotes, MACPF proteins have both lytic and non-lytic roles and function in immunity, invasion and development. The structure and molecular mechanism of several CDCs are relatively well characterized. Pore formation involves oligomerization and assembly of soluble monomers into a ring-shaped pre-pore which undergoes conformational change to insert into membranes, forming a large amphipathic transmembrane β-barrel. In contrast, the structure and mechanism of MACPF proteins has remained obscure. Recent crystallographic studies now reveal that although MACPF and CDCs are extremely divergent at the sequence level, they share a common fold. Together with biochemical studies, these structural data suggest that lytic MACPF proteins use a CDC-like mechanism of membrane disruption, and will help understand the roles these proteins play in immunity and development.
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