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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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Detalles Bibliográficos
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
Descripción
Sumario: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]