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

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 o...

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Published in:PloS one 2014-09, Vol.9 (9), p.e107168-e107168
Main Authors: Yeo, Kwon Joo, Hong, Young-Soo, Jee, Jun-Goo, Lee, Jae Kyoung, Kim, Hyo Jeong, Park, Jin-Wan, Kim, Eun-Hee, Hwang, Eunha, Kim, Sang-Yoon, Lee, Eun-Gyeong, Kwon, Ohsuk, Cheong, Hae-Kap
Format: Article
Language:English
Subjects:
Antibiotics
Bacteria
Biochemistry
Biology and Life Sciences
Biosynthesis
Biotechnology
Deoxyribonucleic acid
DNA
Gene expression
Histidine
Histidine Kinase
Hydrogen-Ion Concentration
In vivo methods and tests
Kinases
Metabolites
NMR
Nuclear magnetic resonance
pH effects
Physiological aspects
Plant metabolites
Protein folding
Protein Kinases - metabolism
Protein structure
Protein Structure, Tertiary
Proteins
Residues
Science
Secondary metabolites
Sensors
Signal transduction
Signal Transduction - physiology
Streptomyces
Streptomyces coelicolor
Streptomyces coelicolor - metabolism
Synthetic biology
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0107168