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Hybrid histidine kinase activation by cyclic di-GMP-mediated domain liberation

Dubey, Badri N. and Agustoni, Elia and Böhm, Raphael and Kaczmarczyk, Andreas and Mangia, Francesca and von Arx, Christoph and Jenal, Urs and Hiller, Sebastian and Plaza-Menacho, Iván and Schirmer, Tilman. (2020) Hybrid histidine kinase activation by cyclic di-GMP-mediated domain liberation. Proceedings of the National Academy of Sciences of the United States of America, 117 (2). pp. 1000-1008.

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Abstract

Cytosolic hybrid histidine kinases (HHKs) constitute major signaling nodes that control various biological processes, but their input signals and how these are processed are largely unknown. In; Caulobacter crescentus; , the HHK ShkA is essential for accurate timing of the G1-S cell cycle transition and is regulated by the corresponding increase in the level of the second messenger c-di-GMP. Here, we use a combination of X-ray crystallography, NMR spectroscopy, functional analyses, and kinetic modeling to reveal the regulatory mechanism of ShkA. In the absence of c-di-GMP, ShkA predominantly adopts a compact domain arrangement that is catalytically inactive. C-di-GMP binds to the dedicated pseudoreceiver domain Rec1, thereby liberating the canonical Rec2 domain from its central position where it obstructs the large-scale motions required for catalysis. Thus, c-di-GMP cannot only stabilize domain interactions, but also engage in domain dissociation to allosterically invoke a downstream effect. Enzyme kinetics data are consistent with conformational selection of the ensemble of active domain constellations by the ligand and show that autophosphorylation is a reversible process.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Hiller)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Dubey, Badri Nath and Agustoni, Elia and Böhm, Raphael and Kaczmarczyk, Andreas and Mangia, Francesca and von Arx, Christoph and Jenal, Urs
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
ISSN:0027-8424
e-ISSN:1091-6490
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:04 Feb 2020 14:10
Deposited On:13 Jan 2020 09:09

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