Evidence map›Paper›PMID 33170270›Full record

ArticleNucleic acids research2020

Structural distinctions between NAD+ riboswitch domains 1 and 2 determine differential folding and ligand binding.

Hao Chen, Michaela Egger, Xiaochen Xu, Laurin Flemmich, Olga Krasheninina, Aiai Sun, Ronald Micura, Aiming Ren

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Full-Length NADBiochemistry · 2023
    Article
  6. Review
  7. Riboswitches, from cognition to transformation.Synthetic and systems biotechnology · 2023
    Review
  8. Review
  9. Article
  10. Discovering riboswitches: the past and the future.Trends in biochemical sciences · 2023
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Hao ChenLife Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Michaela EggerInstitute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.
Xiaochen XuLife Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Laurin FlemmichInstitute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.
Olga KrashenininaInstitute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.
Aiai SunSchool of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.
Ronald MicuraInstitute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, 6020, Austria.
Aiming RenLife Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Universität Innsbruck · ATZhejiang University · CNUniversity of Chinese Academy of Sciences · CN

Funding

Austrian Science Fund FWF M 2517
6 · The paper itself

Abstract

Riboswitches are important gene regulatory elements frequently encountered in bacterial mRNAs. The recently discovered nadA riboswitch contains two similar, tandemly arrayed aptamer domains, with the first domain possessing high affinity for nicotinamide adenine dinucleotide (NAD+). The second domain which comprises the ribosomal binding site in a putative regulatory helix, however, has withdrawn from detection of ligand-induced structural modulation thus far, and therefore, the identity of the cognate ligand and the regulation mechanism have remained unclear. Here, we report crystal structures of both riboswitch domains, each bound to NAD+. Furthermore, we demonstrate that ligand binding to domain 2 requires significantly higher concentrations of NAD+ (or ADP retaining analogs) compared to domain 1. Using a fluorescence spectroscopic approach, we further shed light on the structural features which are responsible for the different ligand affinities, and describe the Mg2+-dependent, distinct folding and pre-organization of their binding pockets. Finally, we speculate about possible scenarios for nadA RNA gene regulation as a putative two-concentration sensor module for a time-controlled signal that is primed and stalled by the gene regulation machinery at low ligand concentrations (domain 1), and finally triggers repression of translation as soon as high ligand concentrations are reached in the cell (domain 2).

Indexed as

RiboswitchAptamers, NucleotideBinding SitesCations, DivalentCloning, MolecularCrystallography, X-RayEscherichia coliGene ExpressionGenetic VectorsHepatitis Delta VirusLigandsMagnesiumModels, MolecularNADProtein BindingProtein Conformation, alpha-HelicalAptamers, NucleotideCations, DivalentLigandsMagnesiumNADRecombinant ProteinsRibonucleoprotein, U1 Small NuclearRiboswitchRNA, CatalyticU1A protein

Identifiers

PMID33170270
PMCPMC7708056
OpenAlexW3101953172

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.