Two Faces of CwlM, an Essential PknB Substrate, in Mycobacterium tuberculosis.
Two Faces of CwlM, an Essential PknB Substrate, in Mycobacterium tuberculosis.
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DOI：
10.1016/j.celrep.2018.09.004
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发表时间：
2018-10-02
期刊：
影响因子：
8.8
通讯作者：
Mukamolova GV
中科院分区：
文献类型：
--
作者：
Turapov O;Forti F;Kadhim B;Ghisotti D;Sassine J;Straatman-Iwanowska A;Bottrill AR;Moynihan PJ;Wallis R;Barthe P;Cohen-Gonsaud M;Ajuh P;Vollmer W;Mukamolova GV
结核病声称每年有100万人死亡，其主要病原体结核分枝杆菌是一种非常成功的病原体。蛋白激酶B对分枝杆菌的生长起着至关重要的作用。在这里，我们证明了蛋白激酶B缺失的结核分枝杆菌可以正常复制，并能在渗透压保护性介质中合成肽聚糖。产生和耗尽PnuB的分枝杆菌的比较磷蛋白质组学表明，CwlM是合成肽聚糖的重要调节因子，是PnuB的主要底物。我们对结核分枝杆菌cwlM突变体的互补研究支持CwlM磷酸化，认为CwlM磷酸化可能是PknB对分枝杆菌生长至关重要的分子基础。我们证明了生长中的分枝杆菌产生两种形式的CwlM：非磷酸化的膜相关形式和PnuB磷酸化的细胞质形式。此外，我们还发现CwlM的磷酸化形式和非磷酸化形式的伙伴蛋白分别是FhaA和Murj，FhaA是一种叉头相关结构域蛋白，Murj是一种建议的类脂II翻转酶。根据我们的结果，我们提出了一个模型，在该模型中，CwlM潜在地调节肽多糖前体的生物合成及其跨细胞膜的运输。在渗透保护介质中，CwlM是PnuB的主要底物，CwlM的磷酸化控制CwlM在细胞质和细胞膜部分的定位，非磷酸CwlM与FhaA结合，非磷酸CwlM与必需的Murj连接物PnuB相互作用，控制结核分枝杆菌的生长和肽聚糖的生物合成。图拉波夫等人。CwlM是PuncB的主要底物，以两种形式产生：非磷酸化的膜相关CwlM和PnuB磷酸化的细胞质CwlM。磷酸化的CwlM与FhaA结合，而非磷酸化的CwlM与MURJ(MviN)相互作用，Murj(MviN)是一种脂类II翻转酶。
Tuberculosis claims >1 million lives annually, and its causative agent Mycobacterium tuberculosis is a highly successful pathogen. Protein kinase B (PknB) is reported to be critical for mycobacterial growth. Here, we demonstrate that PknB-depleted M. tuberculosis can replicate normally and can synthesize peptidoglycan in an osmoprotective medium. Comparative phosphoproteomics of PknB-producing and PknB-depleted mycobacteria identify CwlM, an essential regulator of peptidoglycan synthesis, as a major PknB substrate. Our complementation studies of a cwlM mutant of M. tuberculosis support CwlM phosphorylation as a likely molecular basis for PknB being essential for mycobacterial growth. We demonstrate that growing mycobacteria produce two forms of CwlM: a non-phosphorylated membrane-associated form and a PknB-phosphorylated cytoplasmic form. Furthermore, we show that the partner proteins for the phosphorylated and non-phosphorylated forms of CwlM are FhaA, a fork head-associated domain protein, and MurJ, a proposed lipid II flippase, respectively. From our results, we propose a model in which CwlM potentially regulates both the biosynthesis of peptidoglycan precursors and their transport across the cytoplasmic membrane. PknB is not critical for M. tuberculosis growth in osmoprotective medium CwlM is the major substrate of PknB Phosphorylation controls localization of CwlM in the cytoplasmic and membrane fractions Phospho-CwlM binds FhaA, and non-phospho-CwlM interacts with the essential MurJ linker PknB controls growth and peptidoglycan biosynthesis in Mycobacterium tuberculosis. Turapov et al. show that CwlM, a major PknB substrate, is produced in two forms: a non-phosphorylated membrane-associated CwlM and a PknB-phosphorylated cytoplasmic CwlM. The phosphorylated CwlM binds FhaA, a fork head-associated domain protein, while non-phosphorylated CwlM interacts with MurJ (MviN), a proposed lipid II flippase.
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影响因子：
6.7
作者：
Kieser KJ;Boutte CC;Kester JC;Baer CE;Barczak AK;Meniche X;Chao MC;Rego EH;Sassetti CM;Fortune SM;Rubin EJ
通讯作者：
Rubin EJ
影响因子：
3.7
作者：
Joyce G;Williams KJ;Robb M;Noens E;Tizzano B;Shahrezaei V;Robertson BD
通讯作者：
Robertson BD
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：
4.8
作者：
Chawla, Yogesh;Upadhyay, Sandeep;Nandicoori, Vinay Kumar
通讯作者：
Nandicoori, Vinay Kumar
影响因子：
10.5
作者：
Kang, CM;Abbott, DW;Husson, RN
通讯作者：
Husson, RN