Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.

中文翻译：

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蛋白激酶 StkP 的 PASTA 重复序列将细胞收缩和肺炎链球菌分离连接起来。


具有胞外 PASTA 重复序列的真核样丝氨酸/苏氨酸激酶 (eSTK) 是细菌细胞分裂的关键膜调节因子。 PASTA 重复序列如何控制 eSTK 激活和功能仍然难以捉摸。使用进化和结构引导方法与细胞成像相结合，我们解开了肺炎链球菌 eSTK StkP 的每个 PASTA 重复序列的作用。虽然三个近膜 PASTA 重复序列充当独立于细胞壁结合激活 StkP 所需的可互换模块，但它们也控制隔膜细胞壁厚度。相比之下，第四个膜远端 PASTA 重复序列指导 StkP 在分裂隔膜处定位，并包含一个特定基序，该基序通过与细胞壁水解酶 LytB 相互作用对最终细胞分离至关重要。我们提出了一个模型，其中 StkP 的胞外四 PASTA 结构域在互连 StkP 内源靶标的磷酸化和间隔细胞壁重塑以允许肺炎球菌的细胞分裂方面发挥双重功能。