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利用耶尔森氏菌工具包探究细菌效应蛋白的细胞效应。

Probing the cellular effects of bacterial effector proteins with the Yersinia toolbox.

机构信息

Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, LMU Munich, Pettenkofer Strasse 9A, 80336 Munich, Germany.

出版信息

Future Microbiol. 2012 Apr;7(4):449-56. doi: 10.2217/fmb.12.16.

DOI:10.2217/fmb.12.16
PMID:22439722
Abstract

The type 3 secretion system (T3SS) is a powerful bacterial nanomachine that is able to modify the host cellular immune defense in favor of the pathogen by injection of effector proteins. In this regard, cellular Rho GTPases such as Rac1, RhoA or Cdc42 are targeted by a large group of T3SS effectors by mimicking cellular guanine exchange factors or GTPase-activating proteins. However, functional analysis of one type of T3SS effector that is translocated by bacterial pathogens is challenging because the T3SS effector repertoire can comprise a large number of proteins with redundant or interfering functions. Therefore, we developed the Yersinia toolbox to either analyze singular effector proteins of Yersinia spp. or different bacterial species in the context of bacterial T3SS injection into cells. Here, we focus on the WxxxE guanine exchange factor mimetic proteins IpgB1, IpgB2 and Map, which activate Rac1, RhoA or Cdc42, respectively, as well as the Rho GTPase inactivators YopE (a GTPase-activating mimetic protein) and YopT (cysteine protease), to generate a toolbox module for Rho GTPase manipulation.

摘要

III 型分泌系统(T3SS)是一种强大的细菌纳米机器,能够通过注射效应蛋白来改变宿主细胞的免疫防御,从而有利于病原体。在这方面,细胞 Rho GTPases(如 Rac1、RhoA 或 Cdc42)是一大组 T3SS 效应子的靶标,这些效应子通过模拟细胞鸟嘌呤核苷酸交换因子或 GTPase 激活蛋白来靶向这些 Rho GTPases。然而,由于细菌病原体转位的一种 T3SS 效应子的功能分析具有挑战性,因为 T3SS 效应子库可以包含大量具有冗余或干扰功能的蛋白质。因此,我们开发了耶尔森氏菌工具包,用于分析耶尔森氏菌属或不同细菌物种的单个效应蛋白,或在细菌 T3SS 注射到细胞中的情况下分析这些效应蛋白。在这里,我们重点关注 WxxxE 鸟嘌呤核苷酸交换因子模拟蛋白 IpgB1、IpgB2 和 Map,它们分别激活 Rac1、RhoA 或 Cdc42,以及 Rho GTPase 失活因子 YopE(一种 GTPase 激活模拟蛋白)和 YopT(半胱氨酸蛋白酶),以生成用于 Rho GTPase 操作的工具包模块。

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Future Microbiol. 2012 Apr;7(4):449-56. doi: 10.2217/fmb.12.16.
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Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):904-9. doi: 10.1073/pnas.252770599. Epub 2003 Jan 21.

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