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Title: | A nucleotide-switch mechanism mediates opposing catalytic activities of Rel enzymes | Authors: | Tamman, Hedvig Van Nerom, Katleen Takada, Hiraku Vandenberk, Niels Scholls, Daniel Polikanov, Yury Hofkens, Johan Talavera, Ariel Hauryliuk, Vasili HENDRIX, Jelle Garcia-Pino, Abel |
Issue Date: | 2020 | Publisher: | NATURE PUBLISHING GROUP | Source: | NATURE CHEMICAL BIOLOGY, 16 (8), p. 834–840 | Abstract: | Bifunctional Rel stringent factors, the most abundant class of RelA/SpoT homologs, are ribosome-associated enzymes that transfer a pyrophosphate from ATP onto the 3 ' of guanosine tri-/diphosphate (GTP/GDP) to synthesize the bacterial alarmone (p)ppGpp, and also catalyze the 3 ' pyrophosphate hydrolysis to degrade it. The regulation of the opposing activities of Rel enzymes is a complex allosteric mechanism that remains an active research topic despite decades of research. We show that a guanine-nucleotide-switch mechanism controls catalysis by Thermus thermophilus Rel (Rel(Tt)). The binding of GDP/ATP opens the N-terminal catalytic domains (NTD) of Rel(Tt) (Rel(Tt)(NTD)) by stretching apart the two catalytic domains. This activates the synthetase domain and allosterically blocks hydrolysis. Conversely, binding of ppGpp to the hydrolase domain closes the NTD, burying the synthetase active site and precluding the binding of synthesis precursors. This allosteric mechanism is an activity switch that safeguards against futile cycles of alarmone synthesis and degradation. | Notes: | Garcia-Pino, A (reprint author), Univ Libre Bruxelles, Fac Sci, Cellular & Mol Microbiol, Brussels, Belgium.; Hauryliuk, V (reprint author), Umea Univ, Dept Mol Biol, Umea, Sweden.; Hauryliuk, V (reprint author), Umea Univ, Lab Mol Infect Med Sweden, Umea, Sweden.; Hendrix, J (reprint author), Katholieke Univ Leuven, Chem Dept, Mol Imaging & Photon, Leuven, Belgium.; Garcia-Pino, A (reprint author), WELBIO, Brussels, Belgium. vasili.hauryliuk@umu.se; jelle.hendrix@uhasselt.be; agarciap@ulb.ac.be |
Other: | Garcia-Pino, A (corresponding author), Univ Libre Bruxelles, Fac Sci, Cellular & Mol Microbiol, Brussels, Belgium; WELBIO, Brussels, Belgium. Hauryliuk, V (corresponding author), Umea Univ, Dept Mol Biol, Umea, Sweden; Umea Univ, Lab Mol Infect Med Sweden, Umea, Sweden. Hendrix, J (corresponding author), Katholieke Univ Leuven, Chem Dept, Mol Imaging & Photon, Leuven, Belgium. vasili.hauryliuk@umu.se; jelle.hendrix@uhasselt.be; agarciap@ulb.ac.be | Keywords: | Single-Molecule Fret;(P)Ppgpp;Protein;Synthetase;Refinement;Precision;Ribosome;Homolog;Domain;Ppgpp | Document URI: | http://hdl.handle.net/1942/31451 | ISSN: | 1552-4450 | e-ISSN: | 1552-4469 | DOI: | 10.1038/s41589-020-0520-2 | ISI #: | WOS:000531782600004 | Rights: | 2020 Springer Nature Limited. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2021 |
Appears in Collections: | Research publications |
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s41589-020-0520-2 (2).pdf Restricted Access | Published version | 4.68 MB | Adobe PDF | View/Open Request a copy |
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