Mechanism of the pH-induced conformational change in the sensor domain of the DraK Histidine kinase via the E83, E105, and E107 residues

PLoS One. 2014 Sep 9;9(9):e107168. doi: 10.1371/journal.pone.0107168. eCollection 2014.

Abstract

The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A) is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Histidine Kinase
  • Hydrogen-Ion Concentration
  • Protein Kinases / metabolism*
  • Protein Structure, Tertiary
  • Signal Transduction / physiology
  • Streptomyces coelicolor / metabolism*

Substances

  • Protein Kinases
  • Histidine Kinase

Grants and funding

This study was supported by a KBSI grant (T34410) to C.H.K. by the Pioneer Research Center Program through the National Research Foundation of Korea (2008-2000225) and the Intelligent Synthetic Biology Center of Global Frontier Project (20110031947), which is funded by the Ministry of Science, ICT & Future Planning, and a grant from the KRIBB Research Initiative Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.