The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division (Retracted Article)
The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division (Retracted Article)
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DOI：
10.1099/mic.0.28630-0
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发表时间：
2006-02-01
期刊：
影响因子：
2.8
通讯作者：
Basu, J
中科院分区：
文献类型：
--
作者：
Dasgupta, A;Datta, P;Basu, J
结核分枝杆菌中由 CRI 的 Rv0014c-Rv0018c 编码的一组基因编码候选细胞分裂蛋白 RodA 和 PBPA、一对丝氨酸/苏氨酸激酶 (STPK)、PknA 和 PknB 以及磷酸酶 PstP。围绕该区域的基因组织在大量分枝杆菌物种中是保守的。本研究表明结核分枝杆菌的重组 PBPA 与苄青霉素结合。耻垢分枝杆菌中其对应物的敲除导致生长受阻和细胞分隔缺陷。结核分枝杆菌表达PBPA后，敲除（PBPA-KO）的表型可以恢复到野生型的表型。 PBPA 与新合成的肽聚糖一起定位于分离核之间的分裂位点。 PBPA 和 PknB 的体内共表达、体外激酶测定和位点特异性诱变证实了 PknB 在 T362 和 T437 上磷酸化 PBPA 的观点。 T437A 突变体不能补充 PBPA-KO。这些研究首次证明PBPA属于B类高分子质量PBP的一个亚类，在细胞分裂和细胞形状维持中发挥着重要作用。 PknB 和 PstP 介导的信号转导可能调节该 PBP 在隔膜上的定位，从而调节隔膜肽聚糖生物合成。
A cluster of genes encoded by CRI's Rv0014c-Rv0018c in Mycobacterium tuberculosis encodes candidate cell division proteins RodA and PBPA, a pair of serine/threonine kinases (STPKs), PknA and PknB, and a phosphatase, PstP. The organization of genes encompassing this region is conserved in a large number of mycobacterial species. This study demonstrates that recombinant PBPA of M. tuberculosis binds benzylpenicillin. Knockout of its counterpart in M. smegmatis resulted in hindered growth and defective cell septation. The phenotype of the knockout (PBPA-KO) could be restored to that of the wild-type upon expression of PBPA of M. tuberculosis. PBPA localized to the division site along with newly synthesized peptidoglycan, between segregated nucleoids. In vivo coexpression of PBPA and PknB, in vitro kinase assays and site-specific mutagenesis substantiated the view that PknB phosphorylates PBPA on T362 and T437. A T437A mutant could not complement PBPA-KO. These studies demonstrate for the first time that PBPA, which belongs to a subclass of class B high-molecular-mass PBPs, plays an important role in cell division and cell shape maintenance. Signal transduction mediated by PknB and PstP likely regulates the positioning of this PBP at the septum, thereby regulating septal peptidoglycan biosynthesis.