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对革兰氏阴性细菌病原体效应蛋白的结构洞察,这些效应蛋白可调节其宿主的磷酸化蛋白质组。

Structural insight into effector proteins of Gram-negative bacterial pathogens that modulate the phosphoproteome of their host.

作者信息

Grishin Andrey M, Beyrakhova Ksenia A, Cygler Miroslaw

机构信息

Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5E5.

出版信息

Protein Sci. 2015 May;24(5):604-20. doi: 10.1002/pro.2636. Epub 2015 Feb 6.

DOI:10.1002/pro.2636
PMID:25565677
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4420512/
Abstract

Invading pathogens manipulate cellular process of the host cell to establish a safe replicative niche. To this end they secrete a spectrum of proteins called effectors that modify cellular environment through a variety of mechanisms. One of the most important mechanisms is the manipulation of cellular signaling through modifications of the cellular phosphoproteome. Phosphorylation/dephosphorylation plays a pivotal role in eukaryotic cell signaling, with ∼ 500 different kinases and ∼ 130 phosphatases in the human genome. Pathogens affect the phosphoproteome either directly through the action of bacterial effectors, and/or indirectly through downstream effects of host proteins modified by the effectors. Here we review the current knowledge of the structure, catalytic mechanism and function of bacterial effectors that modify directly the phosphorylation state of host proteins. These effectors belong to four enzyme classes: kinases, phosphatases, phospholyases and serine/threonine acetylases.

摘要

入侵的病原体操纵宿主细胞的细胞过程以建立一个安全的复制微环境。为此,它们分泌一系列称为效应蛋白的蛋白质,这些效应蛋白通过多种机制改变细胞环境。最重要的机制之一是通过修饰细胞磷酸化蛋白质组来操纵细胞信号传导。磷酸化/去磷酸化在真核细胞信号传导中起关键作用,人类基因组中有约500种不同的激酶和约130种磷酸酶。病原体要么通过细菌效应蛋白的作用直接影响磷酸化蛋白质组,和/或通过效应蛋白修饰的宿主蛋白的下游效应间接影响。在这里,我们综述了目前关于直接改变宿主蛋白磷酸化状态的细菌效应蛋白的结构、催化机制和功能的知识。这些效应蛋白属于四类酶:激酶、磷酸酶、磷酸裂解酶和丝氨酸/苏氨酸乙酰转移酶。

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