TolC - the bacterial exit duct for proteins and drugs
TolC - the bacterial exit duct for proteins and drugs
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DOI：
10.1016/s0014-5793(03)01125-6
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发表时间：
2003-11-27
期刊：
影响因子：
3.5
通讯作者：
Koronakis, V
中科院分区：
文献类型：
--
作者：
Koronakis, V
ToIC结构揭示了大小分子从细菌细胞胞质溶胶穿过两层膜和中间周质进入环境的共同运动机制。三聚体ToIC是一种显著的细胞出口管，其与其他膜蛋白完全不同，包含100埃长的α-桶，其穿过周质空间突出，由跨越外膜的40埃长的β-桶锚定。ToIC的周质入口是关闭的，直到内膜中的底物特异性易位酶的募集触发其向开放状态的转变，这是通过隧道α-螺旋的虹膜样“解旋”实现的。ToIC依赖性机制为毒力蛋白和抗菌药物提供了普遍存在的出口途径，并且它们的保守结构，特别是电负性ToIC入口收缩，可能为多药耐药病原体的抑制剂提供靶点。(C)2003年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The ToIC structure has unveiled a common mechanism for the movement of molecules, large and small, from the bacterial cell cytosol, across two membranes and the intervening periplasm, into the environment. Trimeric ToIC is a remarkable cell exit duct that differs radically from other membrane proteins, comprising a 100-Angstrom long alpha-barrel that projects across the periplasmic space, anchored by a 40-Angstrom long beta-barrel spanning the outer membrane. The periplasmic entrance of ToIC is closed until recruitment by substrate-specific translocases in the inner membrane triggers its transition to the open state, achieved by an iris-like 'untwisting' of the tunnel alpha-helices. ToIC-dependent machineries present ubiquitous exit routes for virulence proteins and antibacterial drugs, and their conserved structure, specifically the electronegative ToIC entrance constriction, may present a target for inhibitors of multidrug-resistant pathogens. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.