Cyclic di-GMP
Encyclopedia
Cyclic di-GMP is a second messenger used in signal transduction in a wide variety of bacteria
. Cyclic di-GMP is not known to be used by eukaryote
s or archaea
. 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 structure, it is a tiny cycle of RNA, containing only two guanine
bases linked by ribose
and phosphate
.
In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by protein
s with diguanylate cyclase
activity. These proteins typically have a characteristic GGDEF
motif, which refers to a conserved sequence of five amino acid
s. Degradation of cyclic di-GMP is effected 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 using cyclic di-GMP, at least in some organisms, include biofilm
formation, motility
and induction of virulence
factors.
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
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. Some diguanylate cyclase enzymes and a cellulose synthase in Gluconacetobacter xylinus 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 inhibited 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
es 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.
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
. Cyclic di-GMP is not known to be used by eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s or archaea
Archaea
The Archaea are a group of single-celled microorganisms. A single individual or species from this domain is called an archaeon...
. 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 structure, it is a tiny cycle of RNA, containing only two guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
bases linked by ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....
and phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
.
In bacteria, certain signals are communicated by synthesizing or degrading cyclic di-GMP. Cyclic di-GMP is synthesized by protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s with diguanylate cyclase
Diguanylate cyclase
In enzymology, diguanylate cyclase, also known as diguanylate kinase , is an enzyme that catalyzes the chemical reaction:2 Guanosine triphosphate ↔ 2 diphosphate + cyclic di-3',5'-guanylate...
activity. These proteins typically have a characteristic GGDEF
GGDEF domain
In molecular biology, the GGDEF domain is a protein domain which appears to be ubiquitous in bacteria and is often linked to a regulatory domain, such as a phosphorylation receiver or oxygen sensing domain. Its function is to synthesize cyclic di-GMP, which is used as an intracellular signalling...
motif, which refers to a conserved sequence of five amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. Degradation of cyclic di-GMP is effected by proteins with phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
activity. These proteins have either an EAL or an HD-GYP amino acid motif.
Processes that are known to be regulated using cyclic di-GMP, at least in some organisms, include biofilm
Biofilm
A biofilm is an aggregate of microorganisms in which cells adhere to each other on a surface. These adherent cells are frequently embedded within a self-produced matrix of extracellular polymeric substance...
formation, motility
Motility
Motility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
and induction of virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
factors.
Cyclic di-GMP levels are regulated using a variety of mechanisms. Many proteins with GGDEF, EAL
EAL domain
In molecular biology, the EAL domain is a conserved protein domain. It is found in diverse bacterial signalling proteins. It is named EAL after its conserved residues. The EAL domain may function as a diguanylate phosphodiesterase. The domain contains many conserved acidic residues that could...
or HD-GYP domains are found with other domains that can receive signals, such as PAS domain
PAS domain
The PAS domain is a protein domain contained in many signaling proteins where it functions as a signal sensor. PAS domains are found in a large number of organisms from bacteria to humans...
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. Some diguanylate cyclase enzymes and a cellulose synthase in Gluconacetobacter xylinus 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 inhibited 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
Riboswitch
In molecular biology, a riboswitch is a part of an mRNA molecule that can directly bind a small target molecule, and whose binding of the target affects the gene's activity. Thus, an mRNA that contains a riboswitch is directly involved in regulating its own activity, in response to the...
es called the cyclic di-GMP-I riboswitch and cyclic di-GMP-II riboswitch
Cyclic di-GMP-II riboswitch
Cyclic 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...
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.