Evidence map›Paper›PMID 27841871›Full record

ArticleNature2017

Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography.

J R Stagno, Y Liu, Y R Bhandari, C E Conrad, S Panja, M Swain, L Fan, G Nelson, C Li, D R Wendel and 28 more

Open access · bronzeAbstract read
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed
21.4field-weighted citation impact, top 1% 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

175 citing papers in PubMed, 308 citations in OpenAlex.

  1. Article
  2. Review
  3. Design and discovery of 'tug-of-war' riboswitches.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Glyoxalase activities of Parkinson's disease relevant protein DJ-1/PARK7: Past discoveries and future perspectives.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Ligand-binding pockets in RNA and where to find them.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Article
  20. Article

115 more citing papers are in PubMed but not listed here.

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

38 authors at 12 institutions in 2 countries.

J R StagnoProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
Y LiuProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
Y R BhandariProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
C E ConradDepartment of Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
S PanjaDepartment of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
M SwainProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
L FanSmall Angle X-ray Scattering Core Facility, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
G NelsonDepartment of Physics, Arizona State University, Tempe, Arizona 85287, USA.
C LiDepartment of Physics, Arizona State University, Tempe, Arizona 85287, USA.
D R WendelProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
T A WhiteCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
J D CoeDepartment of Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
M O WiedornCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
J KnoskaCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
D OberthuerCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
R A TuckeyProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
P YuProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
M DybaProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
S G TarasovProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
U WeierstallCenter for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA.
T D GrantHauptmann-Woodward Medical Research Institute, Buffalo, New York 14203, USA.
C D SchwietersCenter for Information Technology, National Institutes of Health, Bethesda, Maryland 20892-5624, USA.
J ZhangLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
A R Ferré-D'AmaréLaboratory of RNA Biophysics and Cellular Physiology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
P FrommeDepartment of Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
D E DraperDepartment of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, USA.
M LiangLinac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA.
M S HunterLinac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA.
S BoutetLinac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA.
K TanStructural Biology Center, Biosciences Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439, USA.
X ZuoX-ray Science Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois 60439, USA.
X JiMacromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
A BartyCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
N A ZatsepinCenter for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA.
H N ChapmanCenter for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.
J C H SpenceCenter for Applied Structural Discovery, The Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA.
S A WoodsonDepartment of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Y-X WangProtein-Nucleic Acid Interaction Section, Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
Arizona State University · USCenter for Cancer Research · USNational Cancer Institute · USJohns Hopkins University · USNational Institutes of Health · USSLAC National Accelerator Laboratory · USUniversität Hamburg · DEArgonne National Laboratory · USCenter for Free-Electron Laser Science · DEDeutsches Elektronen-Synchrotron DESY · DEFrederick National Laboratory for Cancer Research · USHauptman-Woodward Medical Research Institute · US

Funding

Search for the Structural Basis of Biomacromolecular Function and ActivityZIABC010379 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, YUN XING M · 2009 to 2025
$30.4M
Noncoding RNA structures and interactions in cellular stress responses and immunityZIADK075136 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI ZHANG, JINWEI · 2016 to 2025
$23.2M
RNA: New Antimicrobial StrategiesZIAHL006150 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FERRÉ-D'AMARÉ, ADRIAN · 2012 to 2025
$11.8M
CCR Biophysics Resource CoreZICBC010965 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI TARASOV, SERGEY · 2009 to 2025
$10.5M
Biomedical ImagingZIACT000090 · CIT · CENTER FOR INFORMATION TECHNOLOGY · PI TRUS, BENES L · 2009 to 2018
$7.8M
Femtosecond nano-crystallography of membrane proteinsR01GM095583 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI FROMME, PETRA · 2010 to 2023
$4.3M
European Research Council 609920NIGMS NIH HHS R01 GM095583
6 · The paper itself

Abstract

Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.

Indexed as

Nucleic Acid ConformationRiboswitch5' Untranslated RegionsAptamers, NucleotideCrystallizationCrystallography, X-RayDiffusionElectronsKineticsLasersLigandsModels, MolecularNanotechnologyRNA, BacterialRNA FoldingTime Factors5' Untranslated RegionsAptamers, NucleotideLigandsRiboswitchRNA, Bacterial

Identifiers

PMID27841871
PMCPMC5502819
OpenAlexW2552197008

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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.