title: Structural basis of the mercury(II)-mediated conformational switching of the dual-function transcriptional regulator MerR.
abstract: The mer operon confers bacterial resistance to inorganic mercury (Hg(2+)) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg(2+)-binding. To understand how MerR interacts with Hg(2+) and how Hg(2+)-binding modulates MerR function, we report here the crystal structures of apo and Hg(2+)-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg(2+)-MerR structure offers the first view of a triligated Hg(2+)-thiolate center in a metalloprotein, confirming that MerR binds Hg(2+) via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg(2+) binding site, thereby providing a structural basis for the Hg(2+)-mediated functional switching of MerR. The pronounced Hg(2+)-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon.
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zou
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan Agricultural Biotechnology Centre, National Chung Hsing University, Taichung 402, Taiwan cchuang@dragon.nchu.edu.tw.
authors.forename: Chieh-Chen
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan Institute of Biochemistry, College of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan Agricultural Biotechnology Centre, National Chung Hsing University, Taichung 402, Taiwan nlchan@ntu.edu.tw.
authors.forename: Nei-Li
authors.initials: NL
authors.lastname: Chan
mesh_terms: D001410:Bacillus megaterium / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008628:Mercury / Q000737:chemistry*; D008958:Models, Molecular; D009876:Operon; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry*; D015534:Trans-Activators / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C051124:MerR protein, Bacteria; D012097:Repressor Proteins; D015534:Trans-Activators; D008628:Mercury