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A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases.

Publication ,  Journal Article
Liu, Y; Rose, J; Huang, S; Hu, Y; Wu, Q; Wang, D; Li, C; Liu, M; Zhou, P; Jiang, L
Published in: Nat Commun
December 13, 2017

Histidine kinases are key regulators in the bacterial two-component systems that mediate the cellular response to environmental changes. The vast majority of the sensor histidine kinases belong to the bifunctional HisKA family, displaying both kinase and phosphatase activities toward their substrates. The molecular mechanisms regulating the opposing activities of these enzymes are not well understood. Through a combined NMR and crystallographic study on the histidine kinase HK853 and its response regulator RR468 from Thermotoga maritima, here we report a pH-mediated conformational switch of HK853 that shuts off its phosphatase activity under acidic conditions. Such a pH-sensing mechanism is further demonstrated in the EnvZ-OmpR two-component system from Salmonella enterica in vitro and in vivo, which directly contributes to the bacterial infectivity. Our finding reveals a broadly conserved mechanism that regulates the phosphatase activity of the largest family of bifunctional histidine kinases in response to the change of environmental pH.

Duke Scholars

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 13, 2017

Volume

8

Issue

1

Start / End Page

2104

Location

England

Related Subject Headings

  • Thermotoga maritima
  • Salmonella enterica
  • RAW 264.7 Cells
  • Protein Conformation
  • Protein Binding
  • Phosphoprotein Phosphatases
  • Mutation
  • Models, Molecular
  • Mice
  • Magnetic Resonance Spectroscopy
 

Citation

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Liu, Y., Rose, J., Huang, S., Hu, Y., Wu, Q., Wang, D., … Jiang, L. (2017). A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases. Nat Commun, 8(1), 2104. https://doi.org/10.1038/s41467-017-02310-9
Liu, Yixiang, Joshua Rose, Shaojia Huang, Yangbo Hu, Qiong Wu, Dan Wang, Conggang Li, Maili Liu, Pei Zhou, and Ling Jiang. “A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases.Nat Commun 8, no. 1 (December 13, 2017): 2104. https://doi.org/10.1038/s41467-017-02310-9.
Liu Y, Rose J, Huang S, Hu Y, Wu Q, Wang D, et al. A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases. Nat Commun. 2017 Dec 13;8(1):2104.
Liu, Yixiang, et al. “A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases.Nat Commun, vol. 8, no. 1, Dec. 2017, p. 2104. Pubmed, doi:10.1038/s41467-017-02310-9.
Liu Y, Rose J, Huang S, Hu Y, Wu Q, Wang D, Li C, Liu M, Zhou P, Jiang L. A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases. Nat Commun. 2017 Dec 13;8(1):2104.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

December 13, 2017

Volume

8

Issue

1

Start / End Page

2104

Location

England

Related Subject Headings

  • Thermotoga maritima
  • Salmonella enterica
  • RAW 264.7 Cells
  • Protein Conformation
  • Protein Binding
  • Phosphoprotein Phosphatases
  • Mutation
  • Models, Molecular
  • Mice
  • Magnetic Resonance Spectroscopy