Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety of bacteria.[1] Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in Dictyostelium.[2] The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose.[3]
| |
| Names | |
|---|---|
| Systematic IUPAC name
(2R,3R,3aS,7aR,9R,10R,10aS,14aR)-2,9-Bis(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-3,5,10,12-tetrahydroxyoctahydro-2H,5H,7H,12H-5λ5,12λ5-difuro[3,2-d:3′,2′-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-5,12-dione | |
| Other names
Cyclic diguanylate; 3',5'-Cyclic diguanylic acid; c-di-GMP; 5GP-5GP
| |
| Identifiers | |
3D model (JSmol)
|
|
| ChemSpider | |
PubChem CID
|
|
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C20H24N10O14P2 | |
| Molar mass | 690.09 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
In structure, it is a cycle containing only two guanine bases linked by ribose and phosphate.
Function
editContact with surfaces increases c-di-GMP which increases transcription, translation, and post translation of exopolysaccharides (EPSs) and other extracellular polymeric substance matrix components (see the review by Jenal et al 2017).[4] In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by proteins with diguanylate cyclase activity. These proteins typically have a characteristic GGDEF motif, which refers to a conserved sequence of five amino acids. Degradation of cyclic di-GMP is affected by proteins with phosphodiesterase activity. These proteins have either an EAL or an HD-GYP amino acid motif. Processes that are known to be regulated by cyclic di-GMP, at least in some organisms, include biofilm formation (such as EPS matrices found by Steiner et al 2013),[4] motility (especially the motile-to-sessile transition, see the review by Jenal et al 2017)[4] and virulence factor production.
Regulation
editCyclic di-GMP levels are regulated using a variety of mechanisms. Many proteins with GGDEF, EAL or HD-GYP domains are found with other domains that can receive signals, such as PAS domains. Enzymes that degrade or synthesize cyclic di-GMP are believed to be localized to specific regions of the cell, where they influence receivers in a restricted space.[1] In Gluconacetobacter xylinus, c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase.[3] Some diguanylate cyclase enzymes are allosterically inhibited by cyclic di-GMP.
Cyclic di-GMP levels regulate other processes via a number of mechanisms. The Gluconacetobacter xylinus cellulose synthase is allosterically stimulated by cyclic di-GMP, presenting a mechanism by which cyclic di-GMP can regulate cellulose synthase activity. The PilZ domain has been shown to bind cyclic di-GMP and is believed to be involved in cyclic di-GMP-dependent regulation, but the mechanism by which it does this is unknown. Recent structural studies of PilZ domains from two bacterial species have demonstrated that PilZ domains change conformation drastically upon binding to cyclic di-GMP.[5][6] This leads to the strong inference that conformational changes in PilZ domains allow the activity of targeted effector proteins (such as cellulose synthase) to be regulated by cyclic di-GMP. Riboswitches called the cyclic di-GMP-I riboswitch and cyclic di-GMP-II riboswitch regulate gene expression in response to cyclic di-GMP concentrations in a variety of bacteria, but not all bacteria that are known to use cyclic di-GMP.
Host-association
editCyclic di-GMP has been linked to host-association in multiple Pseudomonas species. In an experiment where Pseudomonas lurida was grown in association with the nematode host Caenorhabditis elegans genetic mutations were observed in certain genes that upregulated c-di-GMP, causing a host specialist morphotype to emerge. The mutations affecting c-di-GMP regulation were uncovered with whole genome sequencing. Genes wspE and wspF from the wsp operon exhibited mutations that upregulated c-di-GMP. Additionally, mutations in the gene rph were determined to also affect c-di-GMP expression, which is a novel discovery because rph has not previously been linked to c-di-GMP regulation.[7]
For a review of c-di-GMP roles in Caulobacter crescentus, Pseudomonas aeruginosa, Komagataeibacter xylinus/Gluconacetobacter xylinus, Myxococcus xanthus, Bdellovibrio bacteriovorus and Pseudomonas fluorescens see Jenal et al 2017.[4]
See also
editReferences
edit- ^ a b Tamayo R, Pratt JT, Camilli A (2007). "Roles of cyclic diguanylate in the regulation of bacterial pathogenesis". Annual Review of Microbiology. 61: 131–148. doi:10.1146/annurev.micro.61.080706.093426. PMC 2776827. PMID 17480182.
- ^ Chen ZH, Schaap P (August 2012). "The prokaryote messenger c-di-GMP triggers stalk cell differentiation in Dictyostelium". Nature. 488 (7413): 680–683. Bibcode:2012Natur.488..680C. doi:10.1038/nature11313. PMC 3939355. PMID 22864416.
- ^ a b Ross P, Weinhouse H, Aloni Y, Michaeli D, Weinberger-Ohana P, Mayer R, et al. (1987). "Regulation of cellulose synthesis in Acetobacter xylinum by cyclic diguanylic acid". Nature. 325 (6101): 279–281. Bibcode:1987Natur.325..279R. doi:10.1038/325279a0. PMID 18990795. S2CID 4305512.
- ^ a b c d Laventie BJ, Jenal U (September 2020). "Surface Sensing and Adaptation in Bacteria". Annual Review of Microbiology. 74 (1). Annual Reviews: 735–760. doi:10.1146/annurev-micro-012120-063427. PMID 32905753. S2CID 221622525.
- ^ Benach J, Swaminathan SS, Tamayo R, Handelman SK, Folta-Stogniew E, Ramos JE, et al. (December 2007). "The structural basis of cyclic diguanylate signal transduction by PilZ domains". The EMBO Journal. 26 (24). European Molecular Biology Organization: 5153–5166. doi:10.1038/sj.emboj.7601918. PMC 2140105. PMID 18034161.
- ^ Ko J, Ryu KS, Kim H, Shin JS, Lee JO, Cheong C, et al. (April 2010). "Structure of PP4397 reveals the molecular basis for different c-di-GMP binding modes by Pilz domain proteins". Journal of Molecular Biology. 398 (1): 97–110. doi:10.1016/j.jmb.2010.03.007. PMID 20226196.
- ^ Obeng N, Czerwinski A, Schütz D, Michels J, Leipert J, Bansept F, et al. (October 2023). "Bacterial c-di-GMP has a key role in establishing host-microbe symbiosis". Nature Microbiology. 8 (10): 1809–1819. doi:10.1038/s41564-023-01468-x. PMC 10522488. PMID 37653009.