Aljghami Mazen E, Barghash Marim M, Majaesic Emily, Bhandari Vaibhav, Houry Walid A
Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
Department of Chemistry, University of Toronto, Toronto, ON, Canada.
Front Mol Biosci. 2022 Dec 1;9:1054408. doi: 10.3389/fmolb.2022.1054408. eCollection 2022.
Proteostasis mechanisms significantly contribute to the sculpting of the proteomes of all living organisms. ClpXP is a central AAA+ chaperone-protease complex present in both prokaryotes and eukaryotes that facilitates the unfolding and subsequent degradation of target substrates. ClpX is a hexameric unfoldase ATPase, while ClpP is a tetradecameric serine protease. Substrates of ClpXP belong to many cellular pathways such as DNA damage response, metabolism, and transcriptional regulation. Crucially, disruption of this proteolytic complex in microbes has been shown to impact the virulence and infectivity of various human pathogenic bacteria. Loss of ClpXP impacts stress responses, biofilm formation, and virulence effector protein production, leading to decreased pathogenicity in cell and animal infection models. Here, we provide an overview of the multiple critical functions of ClpXP and its substrates that modulate bacterial virulence with examples from several important human pathogens.
蛋白质稳态机制对所有生物体蛋白质组的塑造起着重要作用。ClpXP是一种存在于原核生物和真核生物中的核心AAA+伴侣蛋白酶复合物，它促进靶底物的解折叠及随后的降解。ClpX是一种六聚体解折叠酶ATP酶，而ClpP是一种十四聚体丝氨酸蛋白酶。ClpXP的底物属于许多细胞途径，如DNA损伤反应、代谢和转录调控。至关重要的是，已证明微生物中这种蛋白水解复合物的破坏会影响各种人类致病细菌的毒力和传染性。ClpXP的缺失会影响应激反应、生物膜形成和毒力效应蛋白的产生，导致细胞和动物感染模型中的致病性降低。在这里，我们概述了ClpXP及其底物的多种关键功能，这些功能通过几种重要人类病原体的例子来调节细菌毒力。
