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Structure. 2014 Sep 2;22(9):1239-51. doi: 10.1016/j.str.2014.04.019. Epub 2014 Jul 31.

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

Author information

  • 1Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group19104, USA, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 2Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 3Pharmacological Sciences Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 4Biochemistry and Molecular Biophysics Graduate Group19104, USA, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 5Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 6Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 7Department of Pharmaceutical Chemistry, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: william.degrado@ucsf.edu.

Abstract

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.

PMID:
25087511
PMCID:
PMC4322757
DOI:
10.1016/j.str.2014.04.019
[PubMed - indexed for MEDLINE]
Free PMC Article
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