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 C(4)-dicarboxylates depend on typical two-component systems (TCS) consisting of a transmembrane sensor histidine kinase and a cytoplasmic response regulator. The 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 DctBp 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.
Zhou
Yan-Feng
YF
National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871, China.
Nan
Beiyan
B
Nan
Jie
J
Ma
Qingjun
Q
Panjikar
Santosh
S
Liang
Yu-He
YH
Wang
Yiping
Y
Su
Xiao-Dong
XD
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D029382:Dicarboxylic Acid Transporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000378:metabolism*; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016962:Sinorhizobium meliloti / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D029382:Dicarboxylic Acid Transporters; D003998:Dicarboxylic Acids; D029968:Escherichia coli Proteins; D008024:Ligands; C073787:DCTB protein, Sinorhizobium; D011494:Protein Kinases; C460095:CitA protein, E coli; C469359:DcuS protein, E coli