Cyclic di-GMP: second messenger extraordinaire

Abstract

27Cyclic dinucleotides are highly versatile signaling molecules in both prokaryotes and eu-

The diguanylate cyclase GcpA inhibits the production of pectate lyases via the H‐NS protein and RsmB regulatory RNA in Dickeya dadantii

“…It was first discovered as an allosteric activator for cellulose synthase in Gluconacetobacter xylinus (Ross et al , 1987). It is now established that c-di-GMP is involved in the regulation of many cellular activities including biofilm formation, motility, cell cycle, antibiotic production, and virulence (Cotter & Stibitz, 2007, Tamayo et al , 2007, Hengge, 2009, Jenal et al , 2017). The synthesis and hydrolysis of c-di-GMP are catalyzed by diguanylate cyclase (DGC) and c-di-GMP-specific phosphodiesterase (PDE) enzymes, respectively.…”

“…The sophisticated c-di-GMP-mediated signaling network includes transcriptional, post-transcriptional, and post-translational regulation. The regulatory function of c-di-GMP is exerted through the binding of c-di-GMP to a variety of cellular effectors, such as PilZ domain proteins, transcription factors, enzymatically inactive GGDEF, EAL or HD-GYP domain proteins and RNA riboswitches (Römling et al, 2013, Ryan et al , 2012, Jenal et al, 2017, Orr et al , 2016). …”

New Functions and Subcellular Localization Patterns of c-di-GMP Components (GGDEF Domain Proteins) in B. subtilis

“…The consensus of numerous studies implies that an increase in c-di-GMP production correlates with a sessile lifestyle [biofilm (BF) formation], whereas low c-di-GMP levels favor planktonic cell behavior. Specific diguanylate cyclases (DGCs) harbor conserved GGDEF domains and synthesize c-di-GMP from two molecules of guanosine-5′-triphosphate (GTP), whereas specific phosphodiesterases (PDEs, containing either EAL or HD-GYP domains) mediate its degradation into the linear dinucleotide 5′-phosphoguanylyl-(3′,5′)-guanosine (pGpG) and/or GMP (Romling et al, 2013; Jenal et al, 2017). Interestingly, these characteristic domains are frequently combined with diverse N-terminal soluble and/or membrane-integrated domains which are primarily utilized for sensory purposes in order to modulate DGC and PDE activities respectively (Plate and Marletta, 2012; Zahringer et al, 2013).…”

Actinoplanes Swims into the Molecular Age

“…In this regard, it is striking that one gene in A. missouriensis, AMIS55850, encodes a predicted methylaccepting chemotaxis protein that also has a PilZ domain. PilZ domains bind c-di-GMP, and PilZ domain-containing proteins are the best-characterized class of c-di-GMP effector proteins (31). It is therefore tempting to speculate that the Actinoplanes life cycle might combine c-di-GMP-mediated regulation of differentiation, as seen in the streptomycetes, with c-di-GMP-mediated regulation of motility, as seen in the gammaproteobacteria.…”

“…2) (26), and it has been the subject of extensive study in Streptomyces, where it also serves to inhibit entry into development by repressing a large regulon of sporulation genes during vegetative growth (27)(28)(29)(30). In Streptomyces, BldD is a cyclic di-GMP (c-di-GMP) effector protein, and it represses its targets in a manner that depends on its binding to c-di-GMP (29,30), one of the most important and widespread second messengers in bacteria (31). Thus, it is not BldD but a BldD-c-di-GMP complex that blocks differentiation, and the crystal structure of this complex has been determined.…”