Nature:EspFu激發宿主肌動蛋白機器的機制

專題：Nature報導

大腸桿菌菌型O157:H7是大腸桿菌的一種腸出血性菌種，能通過感染小腸上皮層引起嚴重的胃腸疾病。細菌效應子蛋白EspFu能誘導肌動蛋白基座的形成，後者是細菌粘附所需要的。

本期Nature上兩篇相關的論文闡述了EspFu激發宿主肌動蛋白機器的機制。Sallee等人所做的一項生化分析表明，EspFu能激發宿主的WASP (Wiscott–Aldrich syndrome protein)肌動蛋白成核因子家族，這些成核因子正常情況下是由GTP酶Cdc42激發的。Hui-Chun Chen等人從結構角度進行了研究，提供了關於EspFu 和 N-WASP之間的結合互動及其激發的詳細信息。EspFu模仿N-WASP內的一個自抑制元素來誘導其激發，導致肌動蛋白的組裝。這個機制可以確保EspFu專門激發WASP，而不是全部Cdc42目標。（生物谷Bioon.com）

生物谷推薦原始出處：

Nature 454, 1005-1008 (21 August 2008) | doi:10.1038/nature07170

The pathogen protein EspF_U hijacks actin polymerization using mimicry and multivalency

Nathan A. Sallee^1,2, Gonzalo M. Rivera³, John E. Dueber^2,4, 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 EspF_U (also known as TccP) into host cells¹. EspF_U 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, EspF_U consists of five-and-a-half 47-amino-acid repeats. Here we show that a 17-residue motif within this EspF_U 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, EspF_U mimics an autoinhibitory element found within N-WASP. Thus, EspF_U activates N-WASP by competitively disrupting the autoinhibited state. By mimicking an internal regulatory element and not the natural activator, EspF_U 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 EspF_U 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.