Assembly of the transmembrane domain of E. coli PhoQ histidine kinase: implications for signal transduction from molecular simulations

PLoS Comput Biol. 2013;9(1):e1002878. doi: 10.1371/journal.pcbi.1002878. Epub 2013 Jan 24.

Abstract

The PhoQP two-component system is a signaling complex essential for bacterial virulence and cationic antimicrobial peptide resistance. PhoQ is the histidine kinase chemoreceptor of this tandem machine and assembles in a homodimer conformation spanning the bacterial inner membrane. Currently, a full understanding of the PhoQ signal transduction is hindered by the lack of a complete atomistic structure. In this study, an atomistic model of the key transmembrane (TM) domain is assembled by using molecular simulations, guided by experimental cross-linking data. The formation of a polar pocket involving Asn202 in the lumen of the tetrameric TM bundle is crucial for the assembly and solvation of the domain. Moreover, a concerted displacement of the TM helices at the periplasmic side is found to modulate a rotation at the cytoplasmic end, supporting the transduction of the chemical signal through a combination of scissoring and rotational movement of the TM helices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Escherichia coli / enzymology*
  • Histidine Kinase
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Models, Molecular*
  • Molecular Dynamics Simulation
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Signal Transduction*

Substances

  • Membrane Proteins
  • Protein Kinases
  • Histidine Kinase

Grant support

This research was supported by the Swiss National Science Foundation (SNSF, grant number 200021_122120). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.