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Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint

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...

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Autores principales: Tamman, Hedvig, Ernits, Karin, Roghanian, Mohammad, Ainelo, Andres, Julius, Christina, Perrier, Anthony, Talavera, Ariel, Ainelo, Hanna, Dugauquier, Rémy, Zedek, Safia, Thureau, Aurelien, Pérez, Javier, Lima-Mendez, Gipsi, Hallez, Régis, Atkinson, Gemma C., Hauryliuk, Vasili, Garcia-Pino, Abel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974481/
https://www.ncbi.nlm.nih.gov/pubmed/36470996
http://dx.doi.org/10.1038/s41589-022-01198-x
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author Tamman, Hedvig
Ernits, Karin
Roghanian, Mohammad
Ainelo, Andres
Julius, Christina
Perrier, Anthony
Talavera, Ariel
Ainelo, Hanna
Dugauquier, Rémy
Zedek, Safia
Thureau, Aurelien
Pérez, Javier
Lima-Mendez, Gipsi
Hallez, Régis
Atkinson, Gemma C.
Hauryliuk, Vasili
Garcia-Pino, Abel
author_facet Tamman, Hedvig
Ernits, Karin
Roghanian, Mohammad
Ainelo, Andres
Julius, Christina
Perrier, Anthony
Talavera, Ariel
Ainelo, Hanna
Dugauquier, Rémy
Zedek, Safia
Thureau, Aurelien
Pérez, Javier
Lima-Mendez, Gipsi
Hallez, Régis
Atkinson, Gemma C.
Hauryliuk, Vasili
Garcia-Pino, Abel
author_sort Tamman, Hedvig
collection PubMed
description 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. [Image: see text]
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spelling pubmed-99744812023-03-02 Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint Tamman, Hedvig Ernits, Karin Roghanian, Mohammad Ainelo, Andres Julius, Christina Perrier, Anthony Talavera, Ariel Ainelo, Hanna Dugauquier, Rémy Zedek, Safia Thureau, Aurelien Pérez, Javier Lima-Mendez, Gipsi Hallez, Régis Atkinson, Gemma C. Hauryliuk, Vasili Garcia-Pino, Abel Nat Chem Biol Article 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. [Image: see text] Nature Publishing Group US 2022-12-05 2023 /pmc/articles/PMC9974481/ /pubmed/36470996 http://dx.doi.org/10.1038/s41589-022-01198-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tamman, Hedvig
Ernits, Karin
Roghanian, Mohammad
Ainelo, Andres
Julius, Christina
Perrier, Anthony
Talavera, Ariel
Ainelo, Hanna
Dugauquier, Rémy
Zedek, Safia
Thureau, Aurelien
Pérez, Javier
Lima-Mendez, Gipsi
Hallez, Régis
Atkinson, Gemma C.
Hauryliuk, Vasili
Garcia-Pino, Abel
Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title_full Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title_fullStr Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title_full_unstemmed Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title_short Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
title_sort structure of spot reveals evolutionary tuning of catalysis via conformational constraint
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9974481/
https://www.ncbi.nlm.nih.gov/pubmed/36470996
http://dx.doi.org/10.1038/s41589-022-01198-x
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