Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking

Badri N. Dubey, Christian Lori, Shogo Ozaki, Geoffrey Fucile, Ivan Plaza-Menacho, Urs Jenal, Tilman Schirmer

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di–guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We demonstrate that both c-di-GMP and ADP (adenosine diphosphate) promote phosphatase activity and propose that c-di-GMP stabilizes the ADP-bound quaternary structure, which allows the receiver domain to access the dimeric DHp stem for dephosphorylation. In silico analyses predict that c-di-GMP control is widespread among bacterial histidine kinases, arguing that it can replace or modulate canonical transmembrane signaling.

Original languageEnglish
Article numbere1600823
JournalScience Advances
Volume2
Issue number9
DOIs
Publication statusPublished - Sep 2016

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Dimerization
Phosphoric Monoester Hydrolases
Histidine
Adenosine Diphosphate
Cell Cycle
Phosphotransferases
Caulobacter crescentus
Second Messenger Systems
Fourier Analysis
Computer Simulation
Catalytic Domain
Phosphorylation
Bacteria
Enzymes
bis(3',5')-cyclic diguanylic acid
Histidine Kinase

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dubey, B. N., Lori, C., Ozaki, S., Fucile, G., Plaza-Menacho, I., Jenal, U., & Schirmer, T. (2016). Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking. Science Advances, 2(9), [e1600823]. https://doi.org/10.1126/sciadv.1600823

Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking. / Dubey, Badri N.; Lori, Christian; Ozaki, Shogo; Fucile, Geoffrey; Plaza-Menacho, Ivan; Jenal, Urs; Schirmer, Tilman.

In: Science Advances, Vol. 2, No. 9, e1600823, 09.2016.

Research output: Contribution to journalArticle

Dubey, BN, Lori, C, Ozaki, S, Fucile, G, Plaza-Menacho, I, Jenal, U & Schirmer, T 2016, 'Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking', Science Advances, vol. 2, no. 9, e1600823. https://doi.org/10.1126/sciadv.1600823
Dubey, Badri N. ; Lori, Christian ; Ozaki, Shogo ; Fucile, Geoffrey ; Plaza-Menacho, Ivan ; Jenal, Urs ; Schirmer, Tilman. / Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking. In: Science Advances. 2016 ; Vol. 2, No. 9.
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