Deciphering the Che2 chemosensory pathway and the roles of individual Che2 proteins from Pseudomonas aeruginosa.

Deciphering the Che2 chemosensory pathway and the roles of individual Che2 proteins from Pseudomonas aeruginosa.
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DOI:
10.1111/mmi.14612
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发表时间:
2021-03
影响因子:
3.6
通讯作者:
Watts KJ
Watts KJ
中科院分区:
生物学2区
文献类型:
--
作者:
Orillard E;Watts KJ

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铜绿假单胞菌是一种机会致病菌,通过四种化学感受系统对其环境进行感知和响应。氧通过与Aer 2受体的PAS-血红素结构域结合来激活Che 2化学感受系统。表面上,Che 2的输出是通过其响应调节器CheY 2发生的,但关于CheY 2的确切作用仍存在争议。在这项研究中,我们表明,CheY 2不相互作用的鞭毛电机和Che 2系统不转移磷酰基的趋化性(车)系统。我们表明,CheY 2,而不是提供反馈控制Aer 2适应。在O2的存在下,Aer 2信号增加组氨酸激酶CheA 2的自磷酸化,然后是CheY 2介导的去磷酸化。CheY 2不稳定地保留磷酸盐,并且可能不发出Che 2系统的输出信号。相反,CheY 2活性增强了CheY 2与适应蛋白CheD的直接相互作用(这一作用通常由CheC促进,而铜绿假单胞菌缺乏)。在没有O2的情况下,Aer 2不发出信号,并且CheY 2/CheD相互作用减弱。这释放了CheD以增强CheR 2介导的Aer 2甲基化,这增强了Aer 2信号传导。CheD不与CheR 2相互作用,但最有可能通过保守的CheD结合基序与Aer 2相互作用,使Aer 2成为更好的甲基化底物。在这项研究中,我们探讨了蛋白质相互作用和磷酸转移反应之间的铜绿假单胞菌的Che 2化学感受蛋白。我们的研究结果支持以下模型:在O2的存在下,Aer 2促进CheA 2自磷酸化,CheY 2介导的去磷酸化,和CheY 2/CheD相互作用。在不存在O2的情况下,Aer 2不发出信号,并且CheD从CheY 2中释放出来以增强CheR 2介导的Aer 2甲基化,这增强了Aer 2信号传导。
Pseudomonas aeruginosa is an opportunistic pathogen that senses and responds to its environment via four chemosensory systems. Oxygen activates the Che2 chemosensory system by binding to the PAS-heme domain of the Aer2 receptor. Ostensibly, the output of Che2 occurs via its response regulator CheY2, but controversy persists over CheY2’s exact role. In this study we show that CheY2 does not interact with the flagellar motor and that the Che2 system does not transfer phosphoryl groups to the chemotaxis (Che) system. We show that CheY2 instead provides feedback control of Aer2 adaptation. In the presence of O2, Aer2 signaling increases the autophosphorylation of the histidine kinase CheA2, followed by CheY2-mediated dephosphorylation. CheY2 does not stably retain phosphate and may not signal the output of the Che2 system. Rather, CheY2 activity enhances the direct interaction of CheY2 with the adaptation protein CheD (a role often facilitated by CheC, which P. aeruginosa lacks). In the absence of O2, Aer2 does not signal, and CheY2/CheD interactions attenuate. This frees CheD to augment CheR2-mediated methylation of Aer2, which enhances Aer2 signaling. CheD does not interact with CheR2, but most likely interacts with Aer2 via conserved CheD-binding motifs to make Aer2 a better methylation substrate. In this study we explored protein interactions and phosphotransfer reactions amongst the Che2 chemosensory proteins of P. aeruginosa. Our results support the following model: In the presence of O2, Aer2 promotes CheA2 autophosphorylation, CheY2-mediated dephosphorylation, and CheY2/CheD interaction. In the absence of O2, Aer2 does not signal and CheD is freed from CheY2 to augment CheR2-mediated methylation of Aer2, which enhances Aer2 signaling.
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