title: Autophosphorylation activity of a soluble hexameric histidine kinase correlates with the shift in protein conformational equilibrium.
abstract: In a commonly accepted model, in response to stimuli, bacterial histidine kinases undergo a conformational transition between an active and inactive form. Structural information on histidine kinases is limited. By using ion mobility-mass spectrometry (IM-MS), we demonstrate an exchange between two conformational populations of histidine kinase ExsG that are linked to different levels of kinase activity. ExsG is an atypical signaling protein that incorporates an uncommon histidine kinase catalytic core at the C terminus preceded by an N-terminal "receiver domain" that is normally associated with the response regulator proteins in two-component signal transduction systems. IM-MS analysis and enzymatic assays indicate that phosphorylation of the ExsG receiver domain stabilizes the "compact" form of the protein and inhibits kinase core activity; in contrast, nucleotide binding required for kinase activity is associated with the more open conformation of ExsG.
authors.affiliation: Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Wojnowska
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Ganesh N
authors.initials: GN
authors.lastname: Sivalingam
authors.forename: Adam
authors.initials: A
authors.lastname: Cryar
authors.forename: Jayesh
authors.initials: J
authors.lastname: Gor
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Thalassinos
authors.forename: Snezana
authors.initials: S
authors.lastname: Djordjevic
mesh_terms: D000071677:Histidine Kinase; D013058:Mass Spectrometry; D010766:Phosphorylation; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: D011494:Protein Kinases; D000071677:Histidine Kinase