ArticleCommunications biology2021
The RelA hydrolase domain acts as a molecular switch for (p)ppGpp synthesis.
Article in Communications biology, 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, 53 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
- The SOS Response: A Double-Edged Sword between the Persister and Resister Formation.ACS omega · 2026Review
- DksA-Dependent Stringent Stress Response Drives Virulence and Gastrointestinal Persistence ofbioRxiv : the preprint server for biology · 2026Article
- NAD+ capping of sibD transcripts in E. coli is mediated by its minimal promoter and enhanced by ppGpp.Nucleic acids research · 2026Article
- Global response to antibiotic exposure reveals a critical role for nucleotide metabolism in high-level β-lactam tolerance.npj antimicrobials and resistance · 2026Article
- Exploring Metalloproteome Remodeling in Calprotectin-StressedACS chemical biology · 2025Article
- Article
- Global response to antibiotic exposure uncovers a critical role for nucleotide metabolism in high-level β-lactam tolerance.Research square · 2025Article
- Characterization of a Novel RNA Polymerase Mutant of Escherichia coli That Confers Thermotolerance and Chaperone Independence.Molecular microbiology · 2025Article
- Symbionts with eroded genomes adjust gene expression according to host life-stage and environment.EMBO reports · 2025Article
- Exploring metalloproteome remodeling in calprotectin-stressedbioRxiv : the preprint server for biology · 2025Article
- Analysis of (p)ppGpp metabolism and signaling using a dynamic luminescent reporter.PLoS genetics · 2025Article
- A novel membrane stress response that blocks chromosomal replication by targeting the DnaA initiator via the ClpP protease.Journal of bacteriology · 2025Article
- Adaptation of a fluoroquinolone-sensitiveRoyal Society open science · 2024Article
- Article
- The Effect of the Stringent Response and Oxidative Stress Response on Fitness Costs of De Novo Acquisition of Antibiotic Resistance.International journal of molecular sciences · 2024Article
- Structure of SpoT reveals evolutionary tuning of catalysis via conformational constraint.Nature chemical biology · 2023Article
- Protein-Ligand Interactions in Scarcity: The Stringent Response from Bacteria to Metazoa, and the Unanswered Questions.International journal of molecular sciences · 2023Review
- Bacterial metabolism and susceptibility to cell wall-active antibiotics.Advances in microbial physiology · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacteria synthesize guanosine tetra- and penta phosphate (commonly referred to as (p)ppGpp) in response to environmental stresses. (p)ppGpp reprograms cell physiology and is essential for stress survival, virulence and antibiotic tolerance. Proteins of the RSH superfamily (RelA/SpoT Homologues) are ubiquitously distributed and hydrolyze or synthesize (p)ppGpp. Structural studies have suggested that the shift between hydrolysis and synthesis is governed by conformational antagonism between the two active sites in RSHs. RelA proteins of γ-proteobacteria exclusively synthesize (p)ppGpp and encode an inactive pseudo-hydrolase domain. Escherichia coli RelA synthesizes (p)ppGpp in response to amino acid starvation with cognate uncharged tRNA at the ribosomal A-site, however, mechanistic details to the regulation of the enzymatic activity remain elusive. Here, we show a role of the enzymatically inactive hydrolase domain in modulating the activity of the synthetase domain of RelA. Using mutagenesis screening and functional studies, we identify a loop region (residues 114-130) in the hydrolase domain, which controls the synthetase activity. We show that a synthetase-inactive loop mutant of RelA is not affected for tRNA binding, but binds the ribosome less efficiently than wild type RelA. Our data support the model that the hydrolase domain acts as a molecular switch to regulate the synthetase activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.