title: Sensing by the membrane-bound sensor kinase DcuS: exogenous versus endogenous sensing of C(4)-dicarboxylates in bacteria.
abstract: Bacteria are able to grow at the expense of both common (succinate, L-malate, fumarate and aspartate) and uncommon (L-tartrate and D-malate) C(4)-dicarboxylates, which are components of central metabolism. Two types of sensors/regulators responding to the C(4)-dicarboxylates function in Escherichia coli, Bacillus, Lactobacillus and related bacteria. The first type represents membrane-integral two-component systems, while the second includes cytoplasmic LysR-type transcriptional regulators. The difference in location and substrate specificity allows the exogenous induction of metabolic genes by common C(4)-dicarboxylates, and endogenous induction by uncommon C(4)-dicarboxylates. The two-component sensors, DcuS and CitA, are composed of an extracellular Per-Arnt-Sim (PAS) domain, two transmembrane helices, a cytoplasmic PAS and the kinase domain. The structures of the extracellular PAS domains of DcuS and CitA have been determined in the ligand-bound and the apo form. Binding of the ligand results in closing and compaction of the binding site, and the structural change gives rise to piston-type movement of the adjacent membrane-spanning helix-2, and signal transmission to the cytoplasmic side. For DcuS, a membrane-embedded construct has been developed that suggests (by experimentation and modeling) that plasticity of the cytoplasmic PAS domain is central to signal transduction from the membrane to the kinase. Sensor kinase DcuS of E. coli requires the C(4)-dicarboxylate transporters DctA or DcuB as co-sensors for function under aerobic and anaerobic conditions, respectively. DcuB contains a regulatory site that controls the function of DcuS and is independent from the transport region. Therefore, DcuS senses C(4)-dicarboxylates in two independent modes, responding to the effector concentration and the metabolic flux of extracellular C(4)-dicarboxylates.
authors.affiliation: Institute for Microbiology & Wine Research, University of Mainz, Germany.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Scheu
authors.forename: Ok Bin
authors.initials: OB
authors.lastname: Kim
authors.forename: Christian
authors.initials: C
authors.lastname: Griesinger
authors.forename: Gottfried
authors.initials: G
authors.lastname: Unden
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D029382:Dicarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D029382:Dicarboxylic Acid Transporters; D003998:Dicarboxylic Acids; D029968:Escherichia coli Proteins; D011494:Protein Kinases; C469359:DcuS protein, E coli