Structure of a type IV secretion system.

Structure of a type IV secretion system.
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DOI:
10.1038/nature13081
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发表时间:
2014-04-24
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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细菌IV型分泌(T4S)系统将毒力因子转运到真核细胞中,在细菌之间分布遗传物质,并已显示出作为人类细胞遗传修饰工具的潜力。考虑到底物通过分泌装置的复杂编排,在缺乏整个机制的结构数据的情况下,T4S系统的分子机制被证明是难以解剖的。本研究利用电子显微镜(EM)对大肠杆菌R388结合质粒编码的T4S系统进行了重构。我们发现,八种蛋白质以复杂的化学计量关系组装在一起,形成一个约3兆道尔顿(MDa)的纳米机器,横跨整个细胞包膜。该结构包括一个外膜相关的核心复合体,由中心茎连接到一个实质性的内膜复合体,内膜复合体由12个VirB4 atp酶亚基组成,并排排列成六聚体桶。我们的结果显示分泌系统具有明显不同的结构,因此机制,其他已知的细菌分泌系统。
Bacterial type IV secretion (T4S) systems translocate virulence factors into eukaryotic cells, distribute genetic material between bacteria, and have shown potential as a tool for the genetic modification of human cells. Given the complex choreography of the substrate through the secretion apparatus, the molecular mechanism of the T4S system has proven difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy (EM) to reconstruct the T4S system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form a ~3 megadalton (MDa) nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of twelve VirB4 ATPase subunits organised as side by side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems.
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发表时间: 2013-04-17
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