ArticleBiochimica et biophysica acta. Gene regulatory mechanisms2018
Structure-function comparisons of (p)ppApp vs (p)ppGpp for Escherichia coli RNA polymerase binding sites and for rrnB P1 promoter regulatory responses in vitro.
Article in Biochimica et biophysica acta. Gene regulatory mechanisms, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Prokaryotic homeostasis - a solution to thrive and survive.Frontiers in molecular biosciences · 2025Review
- How to quantify magic spots - a brief overview of (p)ppGpp detection and quantitation methods.Frontiers in molecular biosciences · 2025Review
- Crosstalk between (p)ppGpp and other nucleotide second messengers.Current opinion in microbiology · 2023Review
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Control of transcription elongation and DNA repair by alarmone ppGpp.Nature structural & molecular biology · 2023Article
- 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
- Photoaffinity Capture Compounds to Profile the Magic Spot Nucleotide Interactomes.Angewandte Chemie (International ed. in English) · 2022Article
- The Role of the Universally Conserved ATPase YchF/Ola1 in Translation Regulation during Cellular Stress.Microorganisms · 2021Review
- The extended (p)ppGpp family: New dimensions in Stress response.Current research in microbial sciences · 2021Review
- Regulatory Themes and Variations by the Stress-Signaling Nucleotide Alarmones (p)ppGpp in Bacteria.Annual review of genetics · 2021Review
- 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
- The Dynamic SecYEG Translocon.Frontiers in molecular biosciences · 2021Review
- Four Phosphates at One Blow: Access to Pentaphosphorylated Magic Spot Nucleotides and Their Analysis by Capillary Electrophoresis.The Journal of organic chemistry · 2020Article
- Chromosomal Organization and Regulation of Genetic Function inEcoSal Plus · 2020Article
- Estimates of RelFrontiers in microbiology · 2020Article
- (p)ppGpp: Magic Modulators of Bacterial Physiology and Metabolism.Frontiers in microbiology · 2020Article
- Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Precise regulation of gene expression is crucial for bacteria to respond to changing environmental conditions. In addition to protein factors affecting RNA polymerase (RNAP) activity, second messengers play an important role in transcription regulation, such as well-known effectors of the stringent response: guanosine 5'triphosphate-3'diphosphate and guanosine 3', 5'-bis(diphosphate) [(p)ppGpp]. Although much is known about importance of the 5' and 3' moieties of (p)ppGpp, the role of the guanine base remains somewhat cryptic. Here, we use (p)ppGpp's adenine analogs [(p)ppApp] to investigate how the nucleobase contributes to determine its binding site and transcriptional regulation. We determined X-ray crystal structure of Escherichia coli RNAP-(p)ppApp complex, which shows the analogs bind near the active site and switch regions of RNAP. We have also explored the regulatory effects of (p)ppApp on transcription initiating from the well-studied E. coli rrnB P1 promoter to assess and compare properties of (p)ppApp with (p)ppGpp. We demonstrate that contrary to (p)ppGpp, (p)ppApp activates transcription at this promoter and DksA hinders this effect. Moreover, pppApp exerts a stronger effect than ppApp. We also show that when ppGpp and pppApp are present together, the outcome depends on which one of them was pre-incubated with RNAP first. This behavior suggests a surprising Yin-Yang like reciprocal plasticity of RNAP responses at a single promoter, occasioned simply by pre-exposure to one or the other nucleotide. Our observations underscore the importance of the (p)ppNpp's purine nucleobase for interactions with RNAP, which may lead to a better fundamental understanding of (p)ppGpp regulation of RNAP 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.