title: Structural analysis of ligand stimulation of the histidine kinase NarX.
abstract: Histidine kinase receptors are a large family of membrane-spanning proteins found in many prokaryotes and some eukaryotes. They are a part of two-component signal transduction systems, which each comprise a sensor kinase and a response regulator and are involved with the regulation of many cellular processes. NarX is a histidine kinase receptor that responds to nitrate and nitrite to effect regulation of anaerobic respiration in various bacteria. We present high-resolution X-ray crystal structures of the periplasmic sensor domain from Escherichia coli NarX in a complex with nitrate and in the apo state. Our analysis reveals that nitrate-binding induces conformation changes that result in a piston-type displacement between the N- and C-terminal helices of the periplasmic domain. Such conformational changes might represent a conserved mechanism of signaling in histidine kinases by which ligand binding is communicated across the lipid bilayer.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Jonah
authors.initials: J
authors.lastname: Cheung
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D000071677:Histidine Kinase; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary / Q000502:physiology; D017386:Sequence Homology, Amino Acid
chemical_list: D029968:Escherichia coli Proteins; D008024:Ligands; D009566:Nitrates; D011494:Protein Kinases; D000071677:Histidine Kinase; C074787:narX protein, E coli