ArticleeLife2019
Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- Bacterial growth rate in populations and single cells.Nature microbiology · 2026Review
- Article
- New perspectives on the molecular mechanisms of stress signalling by the nucleotide guanosine tetraphosphate (ppGpp), an emerging regulator of photosynthesis in plants and algae.The New phytologist · 2023Review
- Termination factor Rho mediates transcriptional reprogramming of Bacillus subtilis stationary phase.PLoS genetics · 2023Article
- The many roles of cyclic di-AMP to control the physiology ofmicroLife · 2023Review
- (p)ppGpp - an important player during heat shock response.microLife · 2023Review
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Review
- Evolution of homo-oligomerization of methionine S-adenosyltransferases is replete with structure-function constrains.Protein science : a publication of the Protein Society · 2022Article
- Article
- Diversity of mechanisms to control bacterial GTP homeostasis by the mutually exclusive binding of adenine and guanine nucleotides to IMP dehydrogenase.Protein science : a publication of the Protein Society · 2022Article
- Diverse molecular mechanisms of transcription regulation by the bacterial alarmone ppGpp.Molecular microbiology · 2022Review
- The nucleotide messenger (p)ppGpp is an anti-inducer of the purine synthesis transcription regulator PurR in Bacillus.Nucleic acids research · 2022Article
- The Role of RelA and SpoT on ppGpp Production, Stress Response, Growth Regulation, and Pathogenicity in Xanthomonas campestris pv.Microbiology spectrum · 2021Article
- Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria.Annual review of genetics · 2021Review
- The Alarmone (p)ppGpp Regulates Primer Extension by Bacterial Primase.Journal of molecular biology · 2021Article
- Emerging and divergent roles of pyrophosphorylated nucleotides in bacterial physiology and pathogenesis.PLoS pathogens · 2021Review
- The stringent response and physiological roles of (pp)pGpp in bacteria.Nature reviews. Microbiology · 2021Review
- ppGpp functions as an alarmone in metazoa.Communications biology · 2020Article
- The nucleotide pGpp acts as a third alarmone in Bacillus, with functions distinct from those of (p) ppGpp.Nature communications · 2020Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein-ligand interactions.
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Registered trials
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.