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

Probing the cellular effects of bacterial effector proteins with the Yersinia toolbox.
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DOI:
10.2217/fmb.12.16
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发表时间:
2012-03
影响因子:
3.1
通讯作者:
S. Wölke;J. Heesemann
S. Wölke;J. Heesemann
中科院分区:
生物学3区
文献类型:
--
作者:
S. Wölke;J. Heesemann

文献摘要

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3型分泌系统(T3SS)是一种功能强大的细菌纳米机器,它能通过注射效应蛋白来改变宿主细胞的免疫防御,有利于病原体。在这一点上,细胞内的Rho GTP酶,如rac1,RhoA或CDC42,通过模仿细胞内的鸟嘌呤交换因子或GTP酶激活蛋白而被一大群T3SS效应器靶向。然而,对细菌病原体易位的一种类型的T3SS效应器的功能分析是具有挑战性的,因为T3SS效应器谱系可能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箱,用于分析耶尔森氏菌的单一效应蛋白。或在细菌T3SS注射到细胞中的不同细菌种类的背景下。在这里,我们关注WxxxE鸟嘌呤交换因子模拟蛋白IpgB1,IpgB2和Map,它们分别激活rac1,RhoA或CDC42,以及Rho GTP酶失活子YopE(一种激活GTP酶的模拟蛋白)和YopT(半胱氨酸蛋白酶),以生成一个用于Rho GTP酶操作的工具箱模块。
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.