ArticleNucleic acids research2021
Ribosome association primes the stringent factor Rel for tRNA-dependent locking in the A-site and activation of (p)ppGpp synthesis.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- RelA-mediated (p)ppGpp accumulation links glucose starvation to peptidoglycan synthesis arrest and spherical morphogenesis via PBP2x and FtsX inJournal of bacteriology · 2026Article
- Structural Basis of pppGpp Binding to the N-Terminal Domain of the Bifunctional RelA/SpoT Homolog RelInternational journal of molecular sciences · 2026Article
- Nanobody-mediated control of long RSH Rel and RelA catalysis by restriction of their conformational landscape.Nature communications · 2026Article
- Article
- The stringent response does not influence ribosome pausing in Bacillus subtilis.Nucleic acids research · 2025Article
- Analysis of (p)ppGpp metabolism and signaling using a dynamic luminescent reporter.PLoS genetics · 2025Article
- Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.Nature chemical biology · 2025Article
- Starvation sensing by mycobacterial RelA/SpoT homologue through constitutive surveillance of translation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint.Nature chemical biology · 2023Article
- Review
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- Pseudomonas aeruginosa Citrate Synthase GltA Influences Antibiotic Tolerance and the Type III Secretion System through the Stringent Response.Microbiology spectrum · 2023Article
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- The structure of DarB in complex with RelScience advances · 2023Article
- Physiological importance and role of MgFrontiers in microbiology · 2023Article
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Structural variations between small alarmone hydrolase dimers support different modes of regulation of the stringent response.The Journal of biological chemistry · 2022Article
- New Chemotypes for the Inhibition of (p)ppGpp Synthesis in the Quest for New Antimicrobial Compounds.Molecules (Basel, Switzerland) · 2022Article
- Crosstalk between guanosine nucleotides regulates cellular heterogeneity in protein synthesis during nutrient limitation.PLoS genetics · 2022Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the Gram-positive Firmicute bacterium Bacillus subtilis, amino acid starvation induces synthesis of the alarmone (p)ppGpp by the RelA/SpoT Homolog factor Rel. This bifunctional enzyme is capable of both synthesizing and hydrolysing (p)ppGpp. To detect amino acid deficiency, Rel monitors the aminoacylation status of the ribosomal A-site tRNA by directly inspecting the tRNA's CCA end. Here we dissect the molecular mechanism of B. subtilis Rel. Off the ribosome, Rel predominantly assumes a 'closed' conformation with dominant (p)ppGpp hydrolysis activity. This state does not specifically select deacylated tRNA since the interaction is only moderately affected by tRNA aminoacylation. Once bound to the vacant ribosomal A-site, Rel assumes an 'open' conformation, which primes its TGS and Helical domains for specific recognition and stabilization of cognate deacylated tRNA on the ribosome. The tRNA locks Rel on the ribosome in a hyperactivated state that processively synthesises (p)ppGpp while the hydrolysis is suppressed. In stark contrast to non-specific tRNA interactions off the ribosome, tRNA-dependent Rel locking on the ribosome and activation of (p)ppGpp synthesis are highly specific and completely abrogated by tRNA aminoacylation. Binding pppGpp to a dedicated allosteric site located in the N-terminal catalytic domain region of the enzyme further enhances its synthetase activity.
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