Two component regulatory system


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Two component regulatory system

  1. 1. Two-component regulatory systemIn molecular biology, Two-component systems serve as a basic stimulus-responsecoupling mechanism to allow organisms to sense and respond to changes in manydifferent environmental conditions.[1] They typically consist of a membrane-boundhistidine kinase that senses a specific environmental stimulus and a correspondingresponse regulator that mediates the cellular response, mostly through differentialexpression of target genes.[2] Two component signaling systems are widely occurring inprokaryotes whereas only a few two-component systems have been identified ineukaryotic organisms.[1]Contents 1 Mechanism of action 2 Function 3 Phospho-relay system 4 Histidine kinases 5 See also 6 ReferencesMechanism of actionSignal transduction occurs through the transfer of phosphoryl groups from adenosinetriphosphate (ATP) to a specific histidine residue in the histidine kinases (HK). This is anautophosphorylation reaction. Subsequently the histidine kinase catalyses the transfer ofthe phosphate group on the phosphorylated histidine residues to an aspartic acidresidue on the response regulator (RR). Phosphorylation causes the responseregulators conformation to change, usually activating an attached output domain, whichthen leads to the stimulation (or repression) of expression of target genes. The level ofphosphorylation of the response regulator controls its activity.[3][4] Some HK arebifunctional, catalysing both the phosphorylation and dephosphorylation of their cognateRR. The input stimuli can regulate either the kinase or phosphatase activity of thebifunctional HK.FunctionTwo-component signal transduction systems enable bacteria to sense, respond, andadapt to a wide range of environments, stressors, and growth conditions.[5] Somebacteria can contain up to as many as 200 two-component systems that need tightregulation to prevent unwanted cross-talk.[6] These pathways have been adapted torespond to a wide variety of stimuli, including nutrients, cellular redox state, changes inosmolarity, quorum signals, antibiotics, temperature, chemoattractants, pH and more.[7][8] In E. coli the EnvZ/OmpR osmoregulation system controls the differential expressionof the outer membrane porin proteins OmpF and OmpC.[9] The KdpD sensor kinaseproteins regulate the kdpFABC operon responsible for potassium transport in bacteriaincluding E. coli and Clostridium acetobutylicum.[10] The N-terminal domain of thisprotein forms part of the cytoplasmic region of the protein, which may be the sensordomain responsible for sensing turgor pressure.[11]Phospho-relay systemA variant of the two-component system is the phospho-relay system. Here a hybrid HKautophosphorylates and then transfers the phosphoryl group to an internal receiver
  2. 2. domain, rather than to a separate RR protein. The phosphoryl group is then shuttled tohistidine phosphotransferase (HPT) and subsequently to a terminal RR, which canevoke the desired response.[12][13]Histidine kinasesSignal transducing histidine kinases are the key elements in two-component signaltransduction systems.[14][15] Examples of histidine kinases are EnvZ, which plays acentral role in osmoregulation,[16] and CheA, which plays a central role in thechemotaxis system.[17] Histidine kinases usually have an N-terminal ligand-bindingdomain and a C-terminal kinase domain, but other domains may also be present. Thekinase domain is responsible for the autophosphorylation of the histidine with ATP, thephosphotransfer from the kinase to an aspartate of the response regulator, and (withbifunctional enzymes) the phosphotransfer from aspartyl phosphate back to ADP or towater.[18] The kinase core has a unique fold, distinct from that of the Ser/Thr/Tyr kinasesuperfamily.HKs can be roughly divided into two classes: orthodox and hybrid kinases.[19][20] Mostorthodox HKs, typified by the Escherichia coli EnvZ protein, function as periplasmicmembrane receptors and have a signal peptide and transmembrane segment(s) thatseparate the protein into a periplasmic N-terminal sensing domain and a highlyconserved cytoplasmic C-terminal kinase core. Members of this family, however, havean integral membrane sensor domain. Not all orthodox kinases are membrane bound,e.g., the nitrogen regulatory kinase NtrB (GlnL) is a soluble cytoplasmic HK.[4] Hybridkinases contain multiple phosphodonor and phosphoacceptor sites and use multi-stepphospho-relay schemes instead of promoting a single phosphoryl transfer. In addition tothe sensor domain and kinase core, they contain a CheY-like receiver domain and a His-containing phosphotransfer (HPt) domain.The Hpr Serine/threonine kinase PtsK is the sensor in a multicomponent phosphorelaysystem in control of carbon catabolic repression in bacteria.[21] This kinase in unusual inthat it recognises the tertiary structure of its target and is a member of a novel familyunrelated to any previously described protein phosphorylating enzymes.[21] X-rayanalysis of the full-length crystalline enzyme from Staphylococcus xylosus at a resolutionof 1.95 A shows the enzyme to consist of two clearly separated domains that areassembled in a hexameric structure resembling a three-bladed propeller. The blades areformed by two N-terminal domains each, and the compact central hub assembles the C-terminal kinase domains.[22]