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Inherent regulation of EAL domain-catalyzed hydrolysis of second messenger c-di-GMP

Sundriyal, Amit and Massa, Claudia and Samoray, Dietrich and Zehender, Fabian and Sharpe, Timothy and Jenal, Urs and Schirmer, Tilman. (2014) Inherent regulation of EAL domain-catalyzed hydrolysis of second messenger c-di-GMP. Journal of Biological Chemistry, 289 (10). pp. 6978-6990.

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Official URL: http://edoc.unibas.ch/dok/A6243388

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Abstract

The universal second messenger cyclic di-GMP (cdG) is involved in the regulation of a diverse range of cellular processes in bacteria. The intracellular concentration of the dinucleotide is determined by the opposing actions of diguanylate cyclases (DGCs) and cdG specific phosphodiesterases (PDEs). While most PDEs have accessory domains that are involved in the regulation of their activity, the regulatory mechanism of this class of enzymes has remained unclear. Here, we use biophysical and functional analyses to show that the isolated EAL domain of a PDE from E. coli (YahA) is in a fast thermodynamic monomer - dimer equilibrium, and that the domain is active only in its dimeric state. Furthermore, our data indicate thermodynamic coupling between substrate binding and EAL dimerization with the dimerization affinity being increased about 100-fold upon substrate binding. Crystal structures of the YahA-EAL domain determined under various conditions (apo, Mg(2+), c-di-GMP/Mg(2+) complex) confirm structural coupling between the dimer interface and the catalytic center. The in-built regulatory properties of the EAL domain probably facilitates its modular, functional combination with the diverse repertoire of accessory domains.
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 > Infection Biology
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Biophysics Facility (Sharpe)
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Schirmer)
UniBasel Contributors:Schirmer, Tilman and Jenal, Urs and Sharpe, Timothy
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
e-ISSN:1083-351X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:21 Nov 2017 12:54
Deposited On:25 Apr 2014 08:01

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