Evidence map›Paper›PMID 33711230›Full record

ArticleJournal of the American Chemical Society2021

The Effects of Sodium Ions on Ligand Binding and Conformational States of G Protein-Coupled Receptors-Insights from Mass Spectrometry.

Mark T Agasid, Lars Sørensen, Leonhard H Urner, Jun Yan, Carol V Robinson

Open access · hybridAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 68 citations in OpenAlex.

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  17. Emergence of mass spectrometry detergents for membrane proteomics.Analytical and bioanalytical chemistry · 2023
    Review
  18. Sodium regulates PLC and IPPhysiological reports · 2023
    Article
  19. 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

5 authors at 2 institutions in 3 countries.

Mark T AgasidDepartment of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Lars SørensenGlobal Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, Måløv 2760, Denmark.
Leonhard H UrnerDepartment of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Jun YanGlobal Research Technologies, Novo Nordisk A/S, Novo Nordisk Park, Måløv 2760, Denmark.
Carol V RobinsonDepartment of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.ORCID 0000-0001-7829-5505
Mansfield University · USNovo Nordisk (Denmark) · DK

Funding

Medical Research Council MR/N020413/1Wellcome TrustWellcome Trust 104633/Z/14/Z
6 · The paper itself

Abstract

The use of mass spectrometry to investigate proteins is now well established and provides invaluable information for both soluble and membrane protein assemblies. Maintaining transient noncovalent interactions under physiological conditions, however, remains challenging. Here, using nanoscale electrospray ionization emitters, we establish conditions that enable mass spectrometry of two G protein-coupled receptors (GPCR) from buffers containing high concentrations of sodium ions. For the Class A GPCR, the adenosine 2A receptor, we observe ligand-induced changes to sodium binding of the receptor at the level of individual sodium ions. We find that antagonists promote sodium binding while agonists attenuate sodium binding. These findings are in line with high-resolution X-ray crystallography wherein only inactive conformations retain sodium ions in allosteric binding pockets. For the glucagon receptor (a Class B GPCR) we observed enhanced ligand binding in electrospray buffers containing high concentrations of sodium, as opposed to ammonium acetate buffers. A combination of native and -omics mass spectrometry revealed the presence of a lipophilic negative allosteric modulator. These experiments highlight the advantages of implementing native mass spectrometry, from electrospray buffers containing high concentrations of physiologically relevant salts, to inform on allosteric ions or ligands with the potential to define their roles on GPCR function.

Indexed as

HumansIonsLigandsMass SpectrometryModels, MolecularReceptors, G-Protein-CoupledSodiumIonsLigandsReceptors, G-Protein-CoupledSodium

Identifiers

PMID33711230
PMCPMC7995251
OpenAlexW3133719327

What Socratic 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 Socratic graph.