Evidence map›Paper›PMID 31724949›Full record

ArticleeLife2019

Direct binding of phosphatidylglycerol at specific sites modulates desensitization of a ligand-gated ion channel.

Ailing Tong, John T Petroff, Fong-Fu Hsu, Philipp Am Schmidpeter, Crina M Nimigean, Liam Sharp, Grace Brannigan, Wayland Wl Cheng

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

26 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
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  12. Review
  13. 5-HTACS chemical neuroscience · 2022
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Structure and function at the lipid-protein interface of a pentameric ligand-gated ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Tracking Membrane Protein Dynamics in Real Time.The Journal of membrane biology · 2021
    Review
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 1 country.

Ailing TongDepartment of Anesthesiology, Washington University, Saint Louis, United States.
John T PetroffDepartment of Anesthesiology, Washington University, Saint Louis, United States.
Fong-Fu HsuDepartment of Internal Medicine, Mass Spectrometry Resource, Division of Endocrinology, Diabetes, Metabolism, and Lipid Research, Washington University, Saint Louis, United States.ORCID 0000-0001-5368-0183
Philipp Am SchmidpeterDepartment of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0003-2871-9706
Crina M NimigeanDepartment of Anesthesiology, Weill Cornell Medical College, New York, United States.ORCID 0000-0002-6254-4447
Liam SharpCenter for Computational and Integrative Biology, Rutgers University, Camden, United States.ORCID 0000-0003-3653-949X
Grace BranniganCenter for Computational and Integrative Biology, Rutgers University, Camden, United States.
Wayland Wl ChengDepartment of Anesthesiology, Washington University, Saint Louis, United States.ORCID 0000-0002-9529-9820
Washington University in St. Louis · USCornell University · USRutgers, The State University of New Jersey · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI FUMIHIKO URANO · 2013 to 2026
$27.1M
TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
Structural dynamics in cyclic nucleotide-modulated channelsR01GM124451 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI NIMIGEAN, CRINA M · 2017 to 2024
$3.2M
Characterizing Neurosteroid Binding in the GABA(A) Receptor Using Top-Down Mass SpectrometryK08GM126336 · NIGMS · WASHINGTON UNIVERSITY · PI CHENG, WAYLAND WING-LUN · 2017 to 2019
$544k
American Heart Association 18POST33960309American Heart Association-American Stroke Association 18POST33960309Center for the Investigation of Membrane Excitability Diseases Pilot Research GrantNIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30DK020579NIGMS NIH HHS K08 GM126336NIGMS NIH HHS K08GM126336NIGMS NIH HHS P41GM103422NIGMS NIH HHS R01 GM124451NIGMS NIH HHS R01GM124451
6 · The paper itself

Abstract

Pentameric ligand-gated ion channels (pLGICs) are essential determinants of synaptic transmission, and are modulated by specific lipids including anionic phospholipids. The exact modulatory effect of anionic phospholipids in pLGICs and the mechanism of this effect are not well understood. Using native mass spectrometry, coarse-grained molecular dynamics simulations and functional assays, we show that the anionic phospholipid, 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), preferentially binds to and stabilizes the pLGIC, Erwinia ligand-gated ion channel (ELIC), and decreases ELIC desensitization. Mutations of five arginines located in the interfacial regions of the transmembrane domain (TMD) reduce POPG binding, and a subset of these mutations increase ELIC desensitization. In contrast, a mutation that decreases ELIC desensitization, increases POPG binding. The results support a mechanism by which POPG stabilizes the open state of ELIC relative to the desensitized state by direct binding at specific sites.

Indexed as

Allosteric RegulationDNA Mutational AnalysisLigand-Gated Ion ChannelsMass SpectrometryMolecular Dynamics SimulationPhosphatidylglycerolsProtein BindingProtein ConformationSynaptic Transmission1-palmitoyl-2-oleoylglycero-3-phosphoglycerolLigand-Gated Ion ChannelsPhosphatidylglycerolsdesensitizationmass spectrometrymembrane channelsmolecular biophysicsnonephospholipidsstructural biology

Identifiers

PMID31724949
PMCPMC6855808
OpenAlexW2988473557

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.