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【bio-news】Nature：EspFu激发宿主肌动蛋白机器的机
大肠杆菌菌型O157:H7是大肠杆菌的一种肠出血性菌种，能通过感染小肠上皮层引起严重的胃肠疾病。细菌效应子蛋白EspFu能诱导肌动蛋白基座的形成，后者是细菌粘附所需要的。
本期Nature上两篇相关的论文阐述了EspFu激发宿主肌动蛋白机器的机制。Sallee等人所做的一项生化分析表明，EspFu能激发宿主的WASP (Wiscott–Aldrich syndrome protein)肌动蛋白成核因子家族，这些成核因子正常情况下是由GTP酶Cdc42激发的。Hui-Chun Chen等人从结构角度进行了研究，提供了关于EspFu 和 N-WASP之间的结合互动及其激发的详细信息。EspFu模仿N-WASP内的一个自抑制元素来诱导其激发，导致肌动蛋白的组装。这个机制可以确保EspFu专门激发WASP，而不是全部Cdc42目标。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 454, 1005-1008 (21 August 2008) | doi:10.1038/nature07170
Nathan A. Sallee1,2, Gonzalo M. Rivera3, John E. Dueber2,4, Dan Vasilescu3, R. Dyche Mullins2, Bruce J. Mayer3 & Wendell A. Lim2
Enterohaemorrhagic Escherichia coli attaches to the intestine through actin pedestals that are formed when the bacterium injects its protein EspFU (also known as TccP) into host cells1. EspFU potently activates the host WASP (Wiskott–Aldrich syndrome protein) family of actin-nucleating factors, which are normally activated by the GTPase CDC42, among other signalling molecules. Apart from its amino-terminal type III secretion signal, EspFU consists of five-and-a-half 47-amino-acid repeats. Here we show that a 17-residue motif within this EspFU repeat is sufficient for interaction with N-WASP (also known as WASL). Unlike most pathogen proteins that interface with the cytoskeletal machinery, this motif does not mimic natural upstream activators: instead of mimicking an activated state of CDC42, EspFU mimics an autoinhibitory element found within N-WASP. Thus, EspFU activates N-WASP by competitively disrupting the autoinhibited state. By mimicking an internal regulatory element and not the natural activator, EspFU selectively activates only a precise subset of CDC42-activated processes. Although one repeat is able to stimulate actin polymerization, we show that multiple-repeat fragments have notably increased potency. The activities of these EspFU fragments correlate with their ability to coordinate activation of at least two N-WASP proteins. Thus, this pathogen has used a simple autoinhibitory fragment as a component to build a highly effective actin polymerization machine. [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-01-29 17:14
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