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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. (2019) Hybrid histidine kinase activation by cyclic di-GMP-mediated domain liberation. New Results.

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Official URL: https://edoc.unibas.ch/71666/

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Abstract

Cytosolic hybrid histidine kinases (HHKs) constitute major signalling 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 modelling 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 pseudo-receiver 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 control activity. Enzyme kinetics data are consistent with conformational selection of the ensemble of active domain constellations by the ligand.
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 (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 Kaczmarczyk, Andreas and Böhm, Raphael and Mangia, Francesca and von Arx, Christoph and Jenal, Urs and Hiller Odermatt, Sebastian
Item Type:Working Paper
Publisher:BioRxiv
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
Language:English
Language:English
Language:English
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Last Modified:01 Oct 2019 15:42
Deposited On:01 Oct 2019 15:41

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