title: The Structure of the Periplasmic Sensor Domain of the Histidine Kinase CusS Shows Unusual Metal Ion Coordination at the Dimeric Interface.
abstract: In bacteria, two-component systems act as signaling systems to respond to environmental stimuli. Two-component systems generally consist of a sensor histidine kinase and a response regulator, which work together through histidyl-aspartyl phosphorelay to result in gene regulation. One of the two-component systems in Escherichia coli, CusS-CusR, is known to induce expression of cusCFBA genes at increased periplasmic Cu(I) and Ag(I) concentrations to help maintain metal ion homeostasis. CusS is a membrane-associated histidine kinase with a periplasmic sensor domain connected to the cytoplasmic ATP binding and catalytic domains through two transmembrane helices. The mechanism of how CusS senses increasing metal ion concentrations and activates CusR is not yet known. Here, we present the crystal structure of the Ag(I)-bound periplasmic sensor domain of CusS at a resolution of 2.15 Å. The structure reveals that CusS forms a homodimer with four Ag(I) binding sites per dimeric complex. Two symmetric metal binding sites are found at the dimeric interface, which are each formed by two histidines and one phenylalanine with an unusual cation-π interaction. The other metal ion binding sites are in a nonconserved region within each monomer. Functional analyses of CusS variants with mutations in the metal sites suggest that the metal ion binding site at the dimer interface is more important for function. The structural and functional data provide support for a model in which metal-induced dimerization results in increases in kinase activity in the cytoplasmic domains of CusS.
authors: Department of Chemistry and Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
authors: Trisiani
authors: T
authors: Affandi
authors: Department of Chemistry and Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
authors: Aaron V
authors: AV
authors: Issaian
authors: Department of Chemistry and Biochemistry, University of Arizona , Tucson, Arizona 85721, United States.
authors: Megan M
authors: MM
authors: McEvoy
mesh_terms: D002942:Circular Dichroism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D000071677:Histidine Kinase / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D008670:Metals; D000071677:Histidine Kinase