Jump to Main Content
A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation
- Erbil, W. Kaya, Price, Mark S., Wemmer, David E., Marletta, Michael A.
- Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.47 pp. 19753-19760
- Shewanella oneidensis, eukaryotic cells, guanylate cyclase, heme, histidine kinase, iron, mutants, nitric oxide, nuclear magnetic resonance spectroscopy, operon, oxygen, prokaryotic cells, proteins, signal transduction
- 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 O₂ 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.