Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint
(2023) In Nature Chemical Biology 19(3). p.334-345- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Chemical Biology
- volume
- 19
- issue
- 3
- pages
- 334 - 345
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85143346889
- pmid:36470996
- ISSN
- 1552-4469
- DOI
- 10.1038/s41589-022-01198-x
- language
- English
- LU publication?
- yes
- additional info
- © 2022. The Author(s).
- id
- a66d946e-970e-4e04-bea7-767ff65a51ff
- date added to LUP
- 2022-12-06 18:13:22
- date last changed
- 2024-09-20 05:21:05
@article{a66d946e-970e-4e04-bea7-767ff65a51ff, abstract = {{<p>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.</p>}}, author = {{Tamman, Hedvig and Ernits, Karin and Roghanian, Mohammad and Ainelo, Andres and Julius, Christina and Perrier, Anthony and Talavera, Ariel and Ainelo, Hanna and Dugauquier, Rémy and Zedek, Safia and Thureau, Aurelien and Pérez, Javier and Lima-Mendez, Gipsi and Hallez, Régis and Atkinson, Gemma C and Hauryliuk, Vasili and Garcia-Pino, Abel}}, issn = {{1552-4469}}, language = {{eng}}, number = {{3}}, pages = {{334--345}}, publisher = {{Nature Publishing Group}}, series = {{Nature Chemical Biology}}, title = {{Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint}}, url = {{http://dx.doi.org/10.1038/s41589-022-01198-x}}, doi = {{10.1038/s41589-022-01198-x}}, volume = {{19}}, year = {{2023}}, }