Cyclic di-GMP (also called cyclic diguanylate and c-di-

GMP GMP may refer to: Finance and economics * Gross metropolitan product * Guaranteed maximum price * Guaranteed Minimum Pension Science and technology * GNU Multiple Precision Arithmetic Library, a software library * Granulocyte-macrophage progeni ...

) is a

second messenger Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first m ...

used in signal transduction in a wide variety of

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

. Cyclic di-GMP is not known to be used by archaea, and has only been observed in

eukaryotes Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bact ...

in ''

Dictyostelium ''Dictyostelium'' is a genus of single- and multi-celled eukaryotic, phagotrophic bacterivores. Though they are Protista and in no way fungal, they traditionally are known as "slime molds". They are present in most terrestrial ecosystems a ...

''. 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 ''Komagataeibacter xylinus'' is a species (biology), species of bacteria best known for its ability to produce cellulose, specifically Bacterial cellulose, bacterial cellulose. History and taxonomy The species was first described in 1886 by Adri ...

'' in order to produce

microbial cellulose Bacterial cellulose is an organic compound with the formula produced by certain types of bacteria. While cellulose is a basic structural material of most plants, it is also produced by bacteria, principally of the genera ''Acetobacter'', ''Sarcin ...

. In structure, it is a cycle containing only two

guanine Guanine () (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is c ...

bases linked by

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compou ...

and

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

. Contact with surfaces increases c-di-GMP which increases

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

translation Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...

, and post translation of

exopolysaccharide Extracellular polymeric substances (EPSs) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs establish the functional and structural integrity of biofilms, and are considered the fundamental comp ...

s (EPSs) and other

extracellular polymeric substance Extracellular polymeric substances (EPSs) are natural polymers of high molecular weight secreted by microorganisms into their environment. EPSs establish the functional and structural integrity of biofilms, and are considered the fundamental comp ...

matrix components (see the review by Jenal et al 2017). In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s with

diguanylate cyclase In enzymology, diguanylate cyclase, also known as diguanylate kinase (), is an enzyme that catalysis, catalyzes the chemical reaction: 2 Guanosine triphosphate ↔ 2 diphosphate + cyclic di-3',5'-guanylate The Substrate (biochemistry), substrates ...

activity. These proteins typically have a characteristic GGDEF motif, which refers to a conserved sequence of five

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s. Degradation of cyclic di-GMP is affected by proteins with

phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many o ...

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 A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...

formation (such as EPS matrices found by Steiner et al 2013),

motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...

(especially the motile-to-sessile transition, see the review by Jenal et al 2017) and

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

factor production. Cyclic 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 domain A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capability ...

s. 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. In ''Gluconacetobacter xylinus,'' c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase. 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. 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.

Riboswitch In molecular biology, a riboswitch is a regulatory segment of a messenger RNA molecule that binds a small molecule, resulting in a change in production of the proteins encoded by the mRNA. Thus, an mRNA that contains a riboswitch is directly in ...

es called the

cyclic di-GMP-I riboswitch Cyclic di-GMP-I riboswitches are a class of riboswitch that specifically bind cyclic di-GMP, which is a second messenger that is used in a variety of microbial processes including virulence, motility and biofilm formation. Cyclic di-GMP-I ...

and

cyclic di-GMP-II riboswitch Cyclic di-GMP-II riboswitches (also c-di-GMP-II riboswitches) form a class of riboswitches that specifically bind cyclic di-GMP, a second messenger used in multiple bacterial processes such as virulence, motility and biofilm formation. Cyclic ...

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. For a review of c-di-GMP roles in ''

Caulobacter crescentus ''Caulobacter crescentus'' is a Gram-negative, oligotrophic bacterium widely distributed in fresh water lakes and streams. The taxon is more properly known as ''Caulobacter vibrioides'' (Henrici and Johnson 1935). ''C. crescentus'' is an impo ...

'', ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aer ...

'', ''

Komagataeibacter xylinus ''Komagataeibacter xylinus'' is a species of bacteria best known for its ability to produce cellulose, specifically bacterial cellulose. History and taxonomy The species was first described in 1886 by Adrian John Brown, who identified the bacter ...

''/''Gluconacetobacter xylinus'', ''

Myxococcus xanthus ''Myxococcus xanthus'' is a gram-negative, rod-shaped species of myxobacteria that exhibits various forms of self-organizing behavior in response to environmental cues. Under normal conditions with abundant food, it exists as a predatory, sapro ...

'', ''

Bdellovibrio bacteriovorus ''Bdellovibrio'' is a genus of Gram-negative, obligate aerobic bacteria. One of the more notable characteristics of this genus is that members can prey upon other Gram-negative bacteria and feed on the biopolymers, e.g. proteins and nucleic acid ...

'' and ''

Pseudomonas fluorescens ''Pseudomonas fluorescens'' is a common Gram-negative, rod-shaped bacterium. It belongs to the '' Pseudomonas'' genus; 16S rRNA analysis as well as phylogenomic analysis has placed ''P. fluorescens'' in the ''P. fluorescens'' group within the g ...

'' see Jenal et al 2017.

References

{{DEFAULTSORT:Cyclic Di-Gmp Nucleotides Cyclic nucleotides

See also

References