edoc

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

Dubey, Badri N. and Lori, Christian and Ozaki, Shogo and Fucile, Geoffrey and Plaza-Menacho, Ivan and Jenal, Urs and Schirmer, Tilman. (2016) Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking. Science Advances, 2 (9). e1600823.

[img]
Preview
PDF - Published Version
Available under License CC BY-NC (Attribution-NonCommercial).

1250Kb

Official URL: http://edoc.unibas.ch/44295/

Downloads: Statistics Overview

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Schirmer)
10 Zentrale universitäre Einrichtungen > SciCore
UniBasel Contributors:Schirmer, Tilman and Dubey, Badri Nath and Lori, Christian and Ozaki, Shogo and Fucile, Geoffrey and Jenal, Urs and Plaza Menacho, Ivan
Item Type:Article, refereed
Article Subtype:Research Article
e-ISSN:2375-2548
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:04 May 2017 06:45
Deposited On:25 Oct 2016 13:06

Repository Staff Only: item control page