Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling: The DctA/DcuS and DcuB/DcuS Sensor Complexes of Escherichia coli.

Abstract

Many membrane-bound sensor kinases require accessory proteins for function. The review describes functional control of membrane-bound sensors by transporters. The C4-dicarboxylate sensor kinase DcuS requires the aerobic or anaerobic C4-dicarboxylate transporters DctA or DcuB, respectively, for function and forms DctA/DcuS or DcuB/DcuS sensor complexes. Free DcuS is in the permanent (ligand independent) ON state. The DctA/DcuS and DcuB/DcuS complexes, on the other hand, control expression in response to C4-dicarboxylates. In DctA/DcuS, helix 8b of DctA and the PASC domain of DcuS are involved in interaction. The stimulus is perceived by the extracytoplasmic sensor domain (PASP) of DcuS. The signal is transmitted across the membrane by a piston-type movement of TM2 of DcuS which appears to be pulled (by analogy to the homologous citrate sensor CitA) by compaction of PASP after C4-dicarboxylate binding. In the cytoplasm, the signal is perceived by the PASC domain of DcuS. PASC inhibits together with DctA the kinase domain of DcuS which is released after C4-dicarboxylate binding. DcuS exhibits two modes for regulating expression of target genes. At higher C4-dicarboxylate levels, DcuS is part of the DctA/DcuS complex and in the C4-dicarboxylate-responsive form which stimulates expression of target genes in response to the concentration of the C4-dicarboxylates (catabolic use of C4-dicarboxylates, mode I regulation). At limiting C4-dicarboxylate concentrations (≤0.05mM), expression of DctA drops and free DcuS appears. Free DcuS is in the permanent ON state (mode II regulation) and stimulates low level (C4-dicarboxylate independent) DctA synthesis for DctA/DcuS complex formation and anabolic C4-dicarboxylate uptake.