title: An essential sensor histidine kinase controlled by transmembrane helix interactions with its auxiliary proteins.
abstract: Two-component signal transduction systems with membrane-embedded sensor histidine kinases are believed to recognize environmental signals and transduce this information over the cellular membrane to influence the activity of a transcription factor to which they are mated. The YycG sensor kinase of Bacillus subtilis, containing two transmembrane helices, is subject to a complicated activity-control circuit involving two other proteins with N-terminal transmembrane helices, YycH and YycI. Truncation studies of YycH and YycI demonstrated that the individual transmembrane helices of these proteins are sufficient to adjust YycG activity, indicating that this control is achieved at the membrane level. A replica exchange molecular dynamics computational approach generated in silico structural models of the transmembrane helix complex that informed mutagenesis studies of the YycI transmembrane helix supporting the accuracy of the in silico model. The results predict that signal recognition by any of the extracellular domains of the sensor histidine kinase YycG or the associated proteins YycH and YycI is transmitted across the cellular membrane by subtle alterations in the positions of the helices within the transmembrane complex of the three proteins.
authors.affiliation: Division of Cellular Biology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA. szurmant@scripps.edu
authors.forename: Hendrik
authors.initials: H
authors.lastname: Szurmant
authors.forename: Lintao
authors.initials: L
authors.lastname: Bu
authors.forename: Charles L
authors.initials: CL
authors.lastname: Brooks
authors.forename: James A
authors.initials: JA
authors.lastname: Hoch
mesh_terms: D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000378:metabolism*; D000071677:Histidine Kinase; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D000071677:Histidine Kinase