C4-Dicarboxylates Sensing Mechanism Revealed by the Crystal Structures of DctB Sensor Domain

C-4-dicarboxylates are the major carbon and energy sources during the symbiotic growth of rhizobia. Responses to C4-dicarboxylates depend on typical two-component systems (TCS) consisting of a transmembrane sensor histidine kinase and a cytoplasmic response regulator. DctB-DctD system is the first identified TCS for C-4-dicarboxylates sensing. Direct ligand binding to the sensor domain of DctB is believed to be the first step of the sensing events. In this report, the water-soluble periplasmic sensor domain of Sinorhizobium meliloti DctB (DctBp) was studied, and three crystal structures were solved: the apo protein, a complex with C-4 succinate, and a complex with C-3 malonate. Different from the two structurally known CitA family of carboxylate sensor proteins CitA and DcuS, the structure of DctBp consists of two tandem Per-Arnt-Sim (PAS) domains and one N-terminal helical region. Only the membrane-distal PAS domain was found to bind the ligands, whereas the proximal PAS domain was empty. Comparison of DctB, CitA, and DcuS suggests a detailed stereochemistry of C-4- dicarboxylates ligand perception. The structures of the different ligand binding states of Dctl3p also revealed a series of conformational changes initiated upon ligand binding and propagated to the N-terminal domain responsible for dimerization, providing insights into understanding the detailed mechanism of the signal transduction of TCS histidine kinases. (C) 2008 Elsevier Ltd. All rights reserved.