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Novel mechanistic insights into physiological signaling pathways mediated by mycobacterial Ser/Thr protein kinases
Genes and Immunity ( IF 5 ) Pub Date : 2019-04-25 , DOI: 10.1038/s41435-019-0069-9
Marco Bellinzoni 1 , Anne Marie Wehenkel 1 , Pedro M. Alzari 1 , Rosario Durán 2
Affiliation  

Protein phosphorylation is known to be one of the keystones of signal sensing and transduction in all living organisms. Once thought to be essentially confined to the eukaryotic kingdoms, reversible phosphorylation on serine, threonine, and tyrosine residues, has now been shown to play a major role in many prokaryotes, where the number of Ser/Thr protein kinases (STPKs) equals or even exceeds that of two-component systems. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is one of the most studied organisms for the role of STPK-mediated signaling in bacteria. Driven by the interest and tractability of these enzymes as potential therapeutic targets, extensive studies revealed the remarkable conservation of protein kinases and their cognate phosphatases across evolution, and their involvement in bacterial physiology and virulence. Here, we present an overview of the current knowledge of mycobacterial STPK structures and kinase activation mechanisms, and we then focus on PknB and PknG, two well-characterized STPKs that are essential for the intracellular survival of the bacillus. We summarize the mechanistic evidence that links PknB to the regulation of peptidoglycan synthesis in cell division and morphogenesis, and the major findings that establish PknG as a master regulator of central carbon and nitrogen metabolism. Two decades after the discovery of STPKs in M. tuberculosis, the emerging landscape of O-phosphosignaling is starting to unveil how eukaryotic-like kinases can be engaged in unique, non-eukaryotic-like, signaling mechanisms in mycobacteria.



中文翻译:

对分枝杆菌Ser / Thr蛋白激酶介导的生理信号通路的新机制的见解

众所周知,蛋白质磷酸化是所有活生物体中信号传感和转导的基石之一。曾经被认为基本上仅限于真核生物的王国,丝氨酸,苏氨酸和酪氨酸残基的可逆磷酸化现在被证明在许多原核生物中起着重要作用,在这些原核生物中,Ser / Thr蛋白激酶(STPKs)的数量等于或什至甚至超过了两部分系统。结核分枝杆菌,是结核病的病原体,是STPK介导的细菌信号转导作用最受研究的有机体之一。在这些酶作为潜在治疗靶点的兴趣和易处理性的驱使下,广泛的研究表明蛋白激酶及其同源磷酸酶在整个进化过程中均具有显着的保守性,并且参与了细菌生理和毒力的研究。在这里,我们介绍了分枝杆菌STPK结构和激酶激活机制的当前知识的概述,然后我们重点介绍了PknB和PknG,这是两种充分表征的STPK,它们对于细菌的细胞内存活至关重要。我们总结了将PknB与细胞分裂和形态发生中的肽聚糖合成调控联系起来的机理证据,以及将PknG确立为中央碳和氮代谢的主要调节剂的主要发现。在发现STPK之后的二十年结核分枝杆菌O- phosphosignaling)的新兴领域开始揭示真核生物样激酶如何参与分枝杆菌中独特的,非真核生物样信号传导机制。

更新日期:2019-04-25
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