Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint.

Autor: Tamman H; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium. hedvig.tamman@ulb.be., Ernits K; Department of Experimental Medicine, University of Lund, Lund, Sweden.; Department of Chemistry, Umeå University, Umeå, Sweden.; Department of Molecular Biology, Umeå University, Umeå, Sweden., Roghanian M; Department of Experimental Medicine, University of Lund, Lund, Sweden.; Department of Molecular Biology, Umeå University, Umeå, Sweden.; Departement of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark., Ainelo A; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium., Julius C; Department of Molecular Biology, Umeå University, Umeå, Sweden., Perrier A; Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium.; Bacterial Cell Cycle and Development, Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium., Talavera A; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium., Ainelo H; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium., Dugauquier R; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium.; Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium., Zedek S; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium., Thureau A; Synchrotron SOLEIL, Saint-Aubin - BP 48, Gif sur Yvette, France., Pérez J; Synchrotron SOLEIL, Saint-Aubin - BP 48, Gif sur Yvette, France., Lima-Mendez G; Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium., Hallez R; Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium.; Bacterial Cell Cycle and Development, Biology of Microorganisms Research Unit, Namur Research Institute for Life Science, University of Namur, Namur, Belgium.; WELBIO, Brussels, Belgium., Atkinson GC; Department of Experimental Medicine, University of Lund, Lund, Sweden.; Department of Molecular Biology, Umeå University, Umeå, Sweden., Hauryliuk V; Department of Experimental Medicine, University of Lund, Lund, Sweden. vasili.hauryliuk@med.lu.se.; Department of Molecular Biology, Umeå University, Umeå, Sweden. vasili.hauryliuk@med.lu.se.; University of Tartu, Institute of Technology, Tartu, Estonia. vasili.hauryliuk@med.lu.se., Garcia-Pino A; Cellular and Molecular Microbiology, Faculté des Sciences, Université libre de Bruxelles (ULB), Boulevard du Triomphe, Brussels, Belgium. abel.garcia.pino@ulb.be.; WELBIO, Brussels, Belgium. abel.garcia.pino@ulb.be.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2023 Mar; Vol. 19 (3), pp. 334-345. Date of Electronic Publication: 2022 Dec 05.
DOI: 10.1038/s41589-022-01198-x
Abstrakt: Stringent factors orchestrate bacterial cell reprogramming through increasing the level of the alarmones (p)ppGpp. In Beta- and Gammaproteobacteria, SpoT hydrolyzes (p)ppGpp to counteract the synthetase activity of RelA. However, structural information about how SpoT controls the levels of (p)ppGpp is missing. Here we present the crystal structure of the hydrolase-only SpoT from Acinetobacter baumannii and uncover the mechanism of intramolecular regulation of 'long'-stringent factors. In contrast to ribosome-associated Rel/RelA that adopt an elongated structure, SpoT assumes a compact τ-shaped structure in which the regulatory domains wrap around a Core subdomain that controls the conformational state of the enzyme. The Core is key to the specialization of long RelA-SpoT homologs toward either synthesis or hydrolysis: the short and structured Core of SpoT stabilizes the τ-state priming the hydrolase domain for (p)ppGpp hydrolysis, whereas the longer, more dynamic Core domain of RelA destabilizes the τ-state priming the monofunctional RelA for efficient (p)ppGpp synthesis.
(© 2022. The Author(s).)
Databáze: MEDLINE
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