Cys-scanning disulfide crosslinking and bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ

Structure. 2014 Sep 2;22(9):1239-1251. doi: 10.1016/j.str.2014.04.019. Epub 2014 Jul 31.


Bacteria transduce signals across the membrane using two-component systems (TCSs), consisting of a membrane-spanning sensor histidine kinase and a cytoplasmic response regulator. In gram-negative bacteria, the PhoPQ TCS senses cations and antimicrobial peptides, yet little is known about the structural changes involved in transmembrane signaling. We construct a model of PhoQ signal transduction using Bayesian inference, based on disulfide crosslinking data and homologous crystal structures. The data are incompatible with a single conformation but are instead consistent with two interconverting structures. These states differ in membrane depth of the periplasmic acidic patch and the reciprocal displacement of diagonal helices along the dimer interface. Studies of multiple histidine kinases suggest this repacking might be a common mode of signal transduction in sensor His-kinase receptors. Because a similar scissors model has been ruled out in CheA-linked chemoreceptors, the evidence suggests that sensor His-kinase and CheA-linked receptors possess different signaling mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / physiology
  • Bayes Theorem
  • Computer Simulation
  • Cystine / chemistry*
  • Histidine Kinase
  • Models, Molecular
  • Protein Kinases / chemistry*
  • Protein Kinases / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Structural Homology, Protein


  • Bacterial Proteins
  • PhoQ protein, Bacteria
  • Cystine
  • Protein Kinases
  • Histidine Kinase