Mycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism.
Mycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism.
复制标题
分枝杆菌丝氨酸/苏氨酸磷酸酶PSTP是磷酸调节的，并定位于介导细胞壁代谢的控制。
DOI：
10.1111/mmi.14951
复制
发表时间：
2022-07
影响因子：
3.6
通讯作者：
Boutte, Cara C.
中科院分区：
文献类型：
--
作者：
Shamma, Farah;Rego, E. Hesper;Boutte, Cara C.
分枝杆菌的细胞壁在应对环境压力时受到深刻的调节，这种调节有助于抗生素耐受性。不同细胞壁调节蛋白的可逆磷酸化是细胞壁调节的主要机制。11种丝氨酸/苏氨酸蛋白激酶（STPKs）磷酸化分枝杆菌中许多关键的细胞壁相关蛋白。PstP是唯一的丝氨酸/苏氨酸磷酸酶，但很少有蛋白质已被证实为PstP底物。PstP本身是磷酸化的，但其磷酸化在调节其活性中的作用尚不清楚。在这项研究中，我们的目的是发现新的底物PstP在结核分枝杆菌（Mtb）。我们在体外表明，PstP去磷酸化两个监管机构的肽聚糖在结核病，FhaA和Wag 31。我们还表明，磷酸模拟突变T137 PstP负调节其对细胞壁调节剂FhaA，Wag 31，CwlM，PknB和PknA的催化活性，并在耻垢分枝杆菌（Msmeg）的相应突变导致体内肽聚糖的误调节。我们发现，PstP是本地化的隔膜，这可能会限制其访问某些基板。这些关于PstP调节的发现提供了对分枝杆菌中细胞壁代谢控制的深入了解。
The mycobacterial cell wall is profoundly regulated in response to environmental stresses, and this regulation contributes to antibiotic tolerance. The reversible phosphorylation of different cell wall regulatory proteins is a major mechanism of cell wall regulation. Eleven Serine/Threonine protein kinases (STPKs) phosphorylate many critical cell wall-related proteins in mycobacteria. PstP is the sole serine/ threonine phosphatase, but few proteins have been verified as PstP substrates. PstP is itself phosphorylated but the role of its phosphorylation in regulating its activity has been unclear. In this study we aim to discover novel substrates of PstP in Mycobacterium tuberculosis (Mtb). We show in vitro that PstP dephosphorylates two regulators of peptidoglycan in Mtb, FhaA and Wag31. We also show that a phospho-mimetic mutation of T137 on PstP negatively regulates its catalytic activity against the cell wall regulators FhaA, Wag31, CwlM, PknB and PknA, and that the corresponding mutation in Mycobacterium smegmatis (Msmeg) causes mis-regulation of peptidoglycan in vivo. We show that PstP is localized to the septum, which likely restricts its access to certain substrates. These findings on the regulation of PstP provide insight into the control of cell wall metabolism in mycobacteria.
登录
查看更多内容
影响因子：
6.4
作者：
DeJesus MA;Gerrick ER;Xu W;Park SW;Long JE;Boutte CC;Rubin EJ;Schnappinger D;Ehrt S;Fortune SM;Sassetti CM;Ioerger TR
通讯作者：
Ioerger TR
影响因子：
7.7
作者：
Bradshaw, Niels;Losick, Richard
通讯作者：
Losick, Richard
影响因子：
3.6
作者：
Boitel, B;Ortiz-Lombardía, M;Alzari, PM
通讯作者：
Alzari, PM
影响因子：
4.8
作者：
Baer, Christina E.;Iavarone, Anthony T.;Sassetti, Christopher M.
通讯作者：
Sassetti, Christopher M.
影响因子：
3.1
作者：
Echenique, J;Kadioglu, A;Trombe, MC
通讯作者：
Trombe, MC