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Local c-di-GMP Signaling in the Control of Synthesis of the E. coli Biofilm Exopolysaccharide pEtN-Cellulose.
Journal of Molecular Biology ( IF 5.6 ) Pub Date : 2020-06-11 , DOI: 10.1016/j.jmb.2020.06.006
Anja M Richter 1 , Alexandra Possling 2 , Nadezhda Malysheva 3 , Kaveh P Yousef 4 , Susanne Herbst 2 , Max von Kleist 3 , Regine Hengge 2
Affiliation  

In many bacteria, the biofilm-promoting second messenger c-di-GMP is produced and degraded by multiple diguanylate cyclases (DGC) and phosphodiesterases (PDE), respectively. High target specificity of some of these enzymes has led to theoretical concepts of “local” c-di-GMP signaling. In Escherichia coli K-12, which has 12 DGCs and 13 PDEs, a single DGC, DgcC, is specifically required for the biosynthesis of the biofilm exopolysaccharide pEtN-cellulose without affecting the cellular c-di-GMP pool, but the mechanistic basis of this target specificity has remained obscure. DGC activity of membrane-associated DgcC, which is demonstrated in vitro in nanodiscs, is shown to be necessary and sufficient to specifically activate cellulose biosynthesis in vivo. DgcC and a particular PDE, PdeK (encoded right next to the cellulose operon), directly interact with cellulose synthase subunit BcsB and with each other, thus establishing physical proximity between cellulose synthase and a local source and sink of c-di-GMP. This arrangement provides a localized, yet open source of c-di-GMP right next to cellulose synthase subunit BcsA, which needs allosteric activation by c-di-GMP. Through mathematical modeling and simulation, we demonstrate that BcsA binding from the low cytosolic c-di-GMP pool in E. coli is negligible, whereas a single c-di-GMP molecule that is produced and released in direct proximity to cellulose synthase increases the probability of c-di-GMP binding to BcsA several hundred-fold. This local c-di-GMP signaling could provide a blueprint for target-specific second messenger signaling also in other bacteria where multiple second messenger producing and degrading enzymes exist.



中文翻译:

大肠杆菌生物膜胞外多糖pEtN-纤维素合成控制中的局部c-di-GMP信号传导。

在许多细菌中,促进生物膜的第二信使c-di-GMP分别由多种双鸟苷酸环化酶(DGC)和磷酸二酯酶(PDE)产生和降解。这些酶中某些酶的高靶标特异性导致了“局部” c-di-GMP信号传导的理论概念。在具有12个DGC和13个PDE的大肠杆菌K-12中,生物膜外多糖pEtN-纤维素的生物合成特别需要单个DGC DgcC,而不影响细胞c-di-GMP池,但其机理是这种靶标特异性仍然不清楚。膜相关DgcC的DGC活性在纳米圆盘中已在体外得到证明,被证明对于体内特异性激活纤维素生物合成是必要和充分的。DgcC和特定的PDE PdeK(编码在纤维素操纵子旁边)直接与纤维素合酶亚基BcsB相互作用,并彼此相互作用,从而在纤维素合酶与c-di-GMP的本地来源和汇之间建立了物理接近性。这种布置提供了紧邻纤维素合酶亚基BcsA的c-di-GMP的本地化源,而后者需要c-di-GMP的变构激活。通过数学建模和仿真,我们证明了BCSA从低细胞质C-二GMP池绑定大肠杆菌可以忽略不计,而直接在纤维素合酶附近产生和释放的单个c-di-GMP分子则将c-di-GMP与BcsA结合的可能性增加了数百倍。这种局部c-di-GMP信号传导也可以为存在多个第二信使产生和降解酶的其他细菌中的目标特异性第二信使信号提供蓝图。

更新日期:2020-07-24
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