title: Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein.
abstract: The large majority of histidine kinases (HKs) are multifunctional enzymes having autokinase, phosphotransfer and phosphatase activities, and most of these are transmembrane sensor proteins. Sensor HKs possess conserved cytoplasmic phosphorylation and ATP-binding kinase domains. The different enzymatic activities require participation by one or both of these domains, implying the need for different conformational states. The catalytic domains are linked to the membrane through a coiled-coil segment that sometimes includes other domains. We describe here the first crystal structure of the complete cytoplasmic region of a sensor HK, one from the thermophile Thermotoga maritima in complex with ADPbetaN at 1.9 A resolution. The structure reveals previously unidentified functions for several conserved residues and reveals the relative disposition of domains in a state seemingly poised for phosphotransfer. The structure thereby inspires hypotheses for the mechanisms of autophosphorylation, phosphotransfer and response-regulator dephosphorylation, and for signal transduction through the coiled-coil segment. Mutational tests support the functional relevance of interdomain contacts.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marina
authors.forename: Carey D
authors.initials: CD
authors.lastname: Waldburger
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D000071677:Histidine Kinase; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020124:Thermotoga maritima / Q000378:metabolism; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D006639:Histidine; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D000071677:Histidine Kinase