Cytoplasmic sensing by the inner membrane histidine kinase EnvZ

Yong Hwee Foo, Yunfeng Gao, Hongfang Zhang, Linda J. Kenney

Research output: Contribution to journalReview articlepeer-review

34 Scopus citations


Two-component regulatory systems drive signal transduction in bacteria. The simplest of these employs a membrane sensor kinase and a cytoplasmic response regulator. Environmental sensing is typically coupled to gene regulation. The histidine kinase EnvZ and its cognate response regulator OmpR regulate expression of outer membrane proteins (porins) in response to osmotic stress. We used hydrogen:deuterium exchange mass spectrometry to identify conformational changes in the cytoplasmic domain of EnvZ (EnvZc) that were associated with osmosensing. The osmosensor localized to a seventeen amino acid region of the four-helix bundle of the cytoplasmic domain and flanked the His243 autophosphorylation site. High osmolality increased autophosphorylation of His243, suggesting that these two events were linked. The transmembrane domains were not required for osmosensing, but mutants in the transmembrane domains altered EnvZ activity. A photoactivatable fusion protein composed of EnvZc fused to the fluorophore mEos2 (EnvZc-mEos2) was as capable as EnvZc in supporting OmpR-dependent ompF and ompC transcription. Over-expression of EnvZc reduced activity, indicating that the EnvZ/OmpR system is not robust. Our results support a model in which osmolytes stabilize helix one in the four-helix bundle of EnvZ by increased hydrogen bonding of the peptide backbone, increasing autophosphorylation and downstream signaling. The likelihood that additional histidine kinases use similar cytoplasmic sensing mechanisms is discussed.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalProgress in Biophysics and Molecular Biology
Issue number3
StatePublished - Sep 1 2015
Externally publishedYes


  • Histidine kinase
  • Hydrogen:deuterium exchange mass spectrometry
  • Osmoregulation
  • Robustness
  • Super-resolution microscopy
  • Two-component regulatory system EnvZ/OmpR

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology


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