Evidence map›Paper›PMID 26344198›Full record

ArticleNature2015

Glycine receptor mechanism elucidated by electron cryo-microscopy.

Juan Du, Wei Lü, Shenping Wu, Yifan Cheng, Eric Gouaux

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed
24.7field-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

231 citing papers in PubMed, 421 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Human GlyRα2 pore dynamics in gating and inhibition.Structure (London, England : 1993) · 2026
    Article
  6. Article
  7. Extracellular KNature communications · 2026
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

171 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

5 authors at 3 institutions in 1 country.

Juan DuVollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Wei LüVollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Shenping WuDepartment of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA.
Yifan ChengDepartment of Biochemistry and Biophysics, University of California San Francisco, 600 16th Street, San Francisco, California 94158, USA.
Eric GouauxVollum Institute, Oregon Health &Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Oregon Health & Science University · USUniversity of California, San Francisco · USVollum Institute · US

Funding

Ultrastructure and Single Particle Microscopy CoreP30NS061800 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI AICHER, SUE A · 2009 to 2020
$6.6M
Structural biology of neurotransmitter ion channelsR01GM100400 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI GOUAUX, JAMES E · 2012 to 2020
$2.3M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM100400NINDS NIH HHS P30 NS061800
6 · The paper itself

Abstract

The strychnine-sensitive glycine receptor (GlyR) mediates inhibitory synaptic transmission in the spinal cord and brainstem and is linked to neurological disorders, including autism and hyperekplexia. Understanding of molecular mechanisms and pharmacology of glycine receptors has been hindered by a lack of high-resolution structures. Here we report electron cryo-microscopy structures of the zebrafish α1 GlyR with strychnine, glycine, or glycine and ivermectin (glycine/ivermectin). Strychnine arrests the receptor in an antagonist-bound closed ion channel state, glycine stabilizes the receptor in an agonist-bound open channel state, and the glycine/ivermectin complex adopts a potentially desensitized or partially open state. Relative to the glycine-bound state, strychnine expands the agonist-binding pocket via outward movement of the C loop, promotes rearrangement of the extracellular and transmembrane domain 'wrist' interface, and leads to rotation of the transmembrane domain towards the pore axis, occluding the ion conduction pathway. These structures illuminate the GlyR mechanism and define a rubric to interpret structures of Cys-loop receptors.

Indexed as

Cryoelectron MicroscopyZebrafishAllosteric RegulationAnimalsBinding SitesGlycineIon Channel GatingIvermectinModels, MolecularNeurotransmitter AgentsProtein ConformationProtein SubunitsReceptors, GlycineRotationSignal TransductionStrychnineGlycineIvermectinNeurotransmitter AgentsProtein SubunitsReceptors, GlycineStrychnine

Identifiers

PMID26344198
PMCPMC4659708
OpenAlexW2102431257

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.