Interaction of Penicillin-Binding Protein 2x and Ser/Thr protein kinase StkP, two key players in Streptococcus pneumoniae R6 morphogenesis
Interaction of Penicillin-Binding Protein 2x and Ser/Thr protein kinase StkP, two key players in Streptococcus pneumoniae R6 morphogenesis
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DOI：
10.1111/mmi.12348
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发表时间：
2013-10-01
影响因子：
3.6
通讯作者：
Di Guilmi, A. M.
中科院分区：
文献类型：
--
作者：
Morlot, C.;Bayle, L.;Di Guilmi, A. M.
细菌细胞的生长和分裂需要肽聚糖生物合成酶和细胞形态发生蛋白的协同作用。然而，允许产生适当的细菌形状并因此保持细胞完整性的调节机制在很大程度上仍未被描述，特别是在卵球菌中。最近，肺炎链球菌（StkP）保守的真核样丝氨酸/苏氨酸蛋白激酶被证明在细胞形状和分裂中起重要作用。在这里，我们研究了StkP调控功能的分子机制，并表明它涉及间隔肽聚糖合成的重要参与者之一，青霉素结合蛋白2x （PBP2x）。我们证明StkP和PBP2x直接相互作用，并存在于肺炎链球菌的相同膜相关复合体中。我们进一步表明，它们都在分裂位点显示出分裂后期的定位模式，并且PBP2x的定位取决于StkP的细胞外PASTA结构域的存在。我们证明StkP和PBP2x的相互作用是由它们的细胞外区域介导的，并且在细胞壁片段存在的情况下，复合物的形成受到抑制。这些数据表明StkP在细胞分裂中的作用是通过与PBP2x的相互作用来调节的。
Bacterial cell growth and division require the co-ordinated action of peptidoglycan biosynthetic enzymes and cell morphogenesis proteins. However, the regulatory mechanisms that allow generating proper bacterial shape and thus preserving cell integrity remain largely uncharacterized, especially in ovococci. Recently, the conserved eukaryotic-like Ser/Thr protein kinase of Streptococcus pneumoniae (StkP) was demonstrated to play a major role in cell shape and division. Here, we investigate the molecular mechanisms underlying the regulatory function(s) of StkP and show that it involves one of the essential actors of septal peptidoglycan synthesis, Penicillin-Binding Protein 2x (PBP2x). We demonstrate that StkP and PBP2x interact directly and are present in the same membrane-associated complex in S.pneumoniae. We further show that they both display a late-division localization pattern at the division site and that the positioning of PBP2x depends on the presence of the extracellular PASTA domains of StkP. We demonstrate that StkP and PBP2x interaction is mediated by their extracellular regions and that the complex formation is inhibited in vitro in the presence of cell wall fragments. These data suggest that the role of StkP in cell division is modulated by an interaction with PBP2x.