title: An asymmetry-to-symmetry switch in signal transmission by the histidine kinase receptor for TMAO.
abstract: The osmoregulator trimethylamine-N-oxide (TMAO), commonplace in aquatic organisms, is used as the terminal electron acceptor for respiration in many bacterial species. The TMAO reductase (Tor) pathway for respiratory catalysis is controlled by a receptor system that comprises the TMAO-binding protein TorT, the sensor histidine kinase TorS, and the response regulator TorR. Here we study the TorS/TorT sensor system to gain mechanistic insight into signaling by histidine kinase receptors. We determined crystal structures for complexes of TorS sensor domains with apo TorT and with TorT (TMAO); we characterized TorS sensor associations with TorT in solution; we analyzed the thermodynamics of TMAO binding to TorT-TorS complexes; and we analyzed in vivo responses to TMAO through the TorT/TorS/TorR system to test structure-inspired hypotheses. TorS-TorT(apo) is an asymmetric 2:2 complex that binds TMAO with negative cooperativity to form a symmetric active kinase.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Jason O
authors.initials: JO
authors.lastname: Moore
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008744:Methylamines / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D033903:Periplasmic Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010770:Phosphotransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012996:Solutions; D013816:Thermodynamics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014736:Vibrio parahaemolyticus / Q000737:chemistry* / Q000235:genetics
chemical_list: D029968:Escherichia coli Proteins; D008744:Methylamines; D033903:Periplasmic Proteins; D011994:Recombinant Proteins; D012996:Solutions; C089364:TorR protein, E coli; C098062:TorT protein, E coli; D014157:Transcription Factors; D010089:Oxidoreductases, N-Demethylating; C023186:trimethylamine dehydrogenase; D010770:Phosphotransferases; C103806:TorS protein, E coli; C005855:trimethyloxamine