Evidence map›Paper›PMID 25023280›Full record

ArticleThe Journal of biological chemistry2014

Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.

Dar'ya S Redka, Takefumi Morizumi, Gwendolynne Elmslie, Pranavan Paranthaman, Rabindra V Shivnaraine, John Ellis, Oliver P Ernst, James W Wells

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Allosteric Modulation of GPCRs of Class A by Cholesterol.International journal of molecular sciences · 2021
    Review
  7. Review
  8. Review
  9. Oligomerization of G protein-coupled receptors: Still doubted?Progress in molecular biology and translational science · 2020
    Review
  10. Cryo-EM structure of the native rhodopsin dimer in nanodiscs.The Journal of biological chemistry · 2019
    Article
  11. GPCR homo-oligomerization.Current opinion in cell biology · 2019
    Review
  12. Review
  13. Article
  14. GPCRs and Signal Transducers: Interaction Stoichiometry.Trends in pharmacological sciences · 2018
    Review
  15. Muscarinic receptor oligomerization.Neuropharmacology · 2018
    Review
  16. Review
  17. Article
  18. Graded activation and free energy landscapes of a muscarinic G-protein-coupled receptor.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  19. Molecular Pharmacology of δ-Opioid Receptors.Pharmacological reviews · 2016
    Review
  20. 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.

Dar'ya S RedkaFrom the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
Takefumi Morizumithe Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Gwendolynne Elmsliethe Departments of Psychiatry and Pharmacology, Hershey Medical Center, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, and.
Pranavan ParanthamanFrom the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
Rabindra V ShivnaraineFrom the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
John Ellisthe Departments of Psychiatry and Pharmacology, Hershey Medical Center, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, and johnellis@psu.edu.
Oliver P Ernstthe Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada, the Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada oliver.ernst@utoronto.ca.
James W WellsFrom the Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada, jwells@phm.utoronto.ca.
University of Toronto · CAPenn State Milton S. Hershey Medical Center · USPennsylvania State University · US

Funding

RESPONSES OF SUBPOPULATIONS OF MUSCARINIC RECEPTORSR01AG005214 · NIA · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI ELLIS, JOHN · 1985 to 2011
$2.3M
CIHR MOP97978NIA NIH HHS R01 AG005214NIA NIH HHS R01AG05214
6 · The paper itself

Abstract

G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins.

Indexed as

Blotting, WesternElectrophoresis, Polyacrylamide GelGTP-Binding ProteinsImmunoprecipitationProtein BindingReceptor, Muscarinic M2GTP-Binding ProteinsReceptor, Muscarinic M2AggregationCooperativityG Protein-coupled Receptor (GPCR)G Protein CouplingMembrane ReconstitutionMonomersNanodiscsOligomersPhospholipid VesicleTernary Complex Model

Identifiers

PMID25023280
PMCPMC4148863
OpenAlexW2071388041

What OpenQuestion holds

Textmetadata
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.