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.replica exchange molecular dynamics simulation ͉ signal transduction ͉ YycG ͉ YycH ͉ YycI S ignal transduction across the cell membrane in bacteria is commonly achieved by using two-component signaltransduction systems. A signal-recognition protein, the sensor histidine kinase, is typically a transmembrane (TM) protein with the capability to sense environmental or cellular stimuli and alter its cytoplasmic autokinase activity in response to these signals. Transfer of the kinase phosphoryl group to a regulatory transcription factor activates or represses the expression of its target genes (reviewed in refs. 1 and 2).The YycFG two-component system of Bacillus subtilis is one of only a few signal-transduction systems known to be essential for cell viability in bacterial organisms, and orthologous systems are conserved by the low GϩC Gram-positive bacteria (3). The high-GϩC Gram-positive Actinomyces also conserve an essential two-component system, the MtrAB system (reviewed in ref. 4). Both the YycFG and the MtrAB systems appear to play a role in regulating cell-wall turnover and cell division in their respective organisms, suggesting that most, if not all, Gram-positive organisms have embedded a two-component signal-transduction system in the regulation of these important processes.The YycFG two-component system has been extensively studied in B. subtilis, Staphylococcus aureus, and Streptococcus pneumoniae. Recent work established the YycF regulon (i.e., the genes whose expression is controlled by this system) in these bacteria (5-7). The majority of gene products under YycF control in all three organisms are involved in cell-wall metabolism, although the precise genes differ from organism to organism. In B. subtilis, the essential cell division proteins FtsZ and FtsA are als...

Insight into the sporulation phosphorelay: Crystal structure of the sensor domain of Bacillus subtilis histidine kinase, KinD

“…21,22 Recent NMR structural data and the results from molecular dynamics simulations have essentially confirmed a four-helix bundle arrangement for histidine kinase transmembrane regions. 23,24 The ligand binding may control the relative orientation of these transmembrane helices. 20 Another noncrystallographic dimer in the crystal is formed by monomers with their proximal domains related by a local twofold axis.…”

Kinetic Characterization of the WalRKSpn(VicRK) Two-Component System ofStreptococcus pneumoniae: Dependence of WalKSpn(VicK) Phosphatase Activity on Its PAS Domain

“…The WalK histidine kinases of Streptococcus species have sensing domains that are structurally different from those of Bacillus, Staphylococcus, and most other species (60,84). WalK Bsu , which is typical of one class, contains two transmembrane domains flanking an extracytoplasmic domain.…”

A Life inBacillus subtilisSignal Transduction

“…The results predicted 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, and mutational analysis substantiated the prediction. Moreover, truncation studies of YycH and YycI demonstrated that the individual transmembrane helices of these proteins, lacking the extracellular domains, were sufficient to control YycG activity (81). What the extracellular domains of YycH and YycI are doing is still a mystery.…”