Local c-di-GMP Signaling in the Control of Synthesis of the E. coli Biofilm Exopolysaccharide pEtN-Cellulose

JOURNAL OF MOLECULAR BIOLOGY

卷:432

Article

Richter, Anja M.^1,4  Possling, Alexandra¹  Malysheva, Nadezhda^2,3  Yousef, Kaveh P.²  Herbst, Susanne¹  von Kleist, Max^2,3  Hengge, Regine¹ 

[1] Humboldt Univ, Inst Biol Microbiol, Philippstr 13,Haus 22, D-10115 Berlin, Germany

[2] Free Univ Berlin, Dept Math & Comp Sci, D-14195 Berlin, Germany

[3] Robert Koch Inst, MF1 Bioinformat, D-13353 Berlin, Germany

[4] Bundesanstalt Mat Forsch & Prufung, Dept Mat & Environm, D-12205 Berlin, Germany

关键词: bacterial second messenger;    cellulose synthase;    diguanylate cyclase;    GGDEF domain;   

DOI  :  10.1016/j.jmb.2020.06.006

来源: Elsevier

【 摘 要 】

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. coil 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. (C) 2020 The Authors. Published by Elsevier Ltd.

【 授权许可】

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