title: A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation.
abstract: Heme nitric oxide/oxygen (H-NOX) proteins are found in eukaryotes where they are typically part of a larger protein such as soluble guanylate cyclase and in prokaryotes where they are often found in operons with a histidine kinase, suggesting that H-NOX proteins serve as sensors for NO and O(2) in signaling pathways. The Fe(II)-NO complex of the H-NOX protein from Shewanella oneidensis inhibits the autophosphorylation of the operon-associated histidine kinase, whereas the ligand-free H-NOX has no effect on the kinase. NMR spectroscopy was used to determine the structures of the Fe(II)-CO complex of the S. oneidensis H-NOX and the Fe(II)-CO complex of the H103G H-NOX mutant as a mimic of the ligand-free and kinase-inhibitory Fe(II)-NO H-NOX, respectively. The results provide a molecular glimpse into the ligand-induced conformational changes that may underlie kinase inhibition and the subsequent control of downstream signaling.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720-3220, USA.
authors.forename: W Kaya
authors.initials: WK
authors.lastname: Erbil
authors.forename: Mark S
authors.initials: MS
authors.lastname: Price
authors.forename: David E
authors.initials: DE
authors.lastname: Wemmer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D000071677:Histidine Kinase; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020592:Shewanella / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D006418:Heme; D002248:Carbon Monoxide; D011494:Protein Kinases; D000071677:Histidine Kinase