Sensing by the Membrane-Bound Sensor Kinase DcuS: Exogenous Versus Endogenous Sensing of C₄-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) C₄-dicarboxylates, which are components of central metabolism. Two types of sensors/regulators responding to the C₄-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 C₄-dicarboxylates, and endogenous induction by uncommon C₄-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 C₄-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 C₄-dicarboxylates in two independent modes, responding to the effector concentration and the metabolic flux of extracellular C₄-dicarboxylates.

Keywords:

• C₄-dicarboxylate
• DcuB
• DcuS
• extracellular sensing
• fumarate
• intracellular sensing
• sensor kinase
• succinate
• TtdR

Acknowledgements

The authors thank S Nilkens for reading the manuscript.

Financial & competing interests disclosure

Work in the authors‘ laboratories was supported by grants of Deutsche Forschungsgemeinschaft. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Work in the authors‘ laboratories was supported by grants of Deutsche Forschungsgemeinschaft. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed