title: Mechanism of the pH-induced conformational change in the sensor domain of the DraK Histidine kinase via the E83, E105, and E107 residues.
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.
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chungbuk, Republic of Korea.
authors.forename: Kwon Joo
authors.initials: KJ
authors.lastname: Yeo
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Chungbuk, Republic of Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Kyungpook National University, Kyungpook, Republic of Korea.
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Chungbuk, Republic of Korea.
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Chungbuk, Republic of Korea.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chungbuk, Republic of Korea.
authors.forename: Jin-Wan
authors.initials: JW
authors.lastname: Park
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chungbuk, Republic of Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chungbuk, Republic of Korea.
authors.forename: Eunha
authors.initials: E
authors.lastname: Hwang
authors.affiliation: Biochemicals and Synthetic Biology Research Center, KRIBB, Yuseong-Gu, Daejeon, Republic of Korea.
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Biochemicals and Synthetic Biology Research Center, KRIBB, Yuseong-Gu, Daejeon, Republic of Korea.
authors.forename: Eun-Gyeong
authors.initials: EG
authors.lastname: Lee
authors.affiliation: Biochemicals and Synthetic Biology Research Center, KRIBB, Yuseong-Gu, Daejeon, Republic of Korea.
authors.forename: Ohsuk
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Division of Magnetic Resonance, Korea Basic Science Institute (KBSI), Ochang, Chungbuk, Republic of Korea.
authors.forename: Hae-Kap
authors.initials: HK
authors.lastname: Cheong
mesh_terms: D000071677:Histidine Kinase; D006863:Hydrogen-Ion Concentration; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D048372:Streptomyces coelicolor / Q000378:metabolism*
chemical_list: D011494:Protein Kinases; D000071677:Histidine Kinase