Evidence map›Paper›PMID 30334738›Full record

ArticleeLife2018

Consensus designs and thermal stability determinants of a human glutamate transporter.

Erica Cirri, Sébastien Brier, Reda Assal, Juan Carlos Canul-Tec, Julia Chamot-Rooke, Nicolas Reyes

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

13 citing papers in PubMed, 27 citations in OpenAlex.

  1. Multimodal dynamics control activity of a glial glutamate transporter.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. eGFP as an All-in-One Tag for Purification of Membrane Proteins.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  5. Article
  6. Article
  7. Engineering a HyperstableJournal of the American Chemical Society · 2022
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Consensus mutagenesis approach improves the thermal stability of system xProtein science : a publication of the Protein Society · 2020
    Article
  13. 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

6 authors at 1 institution in 2 countries.

Erica CirriMolecular Mechanisms of Membrane Transport Laboratory, Institut Pasteur, Paris, France.
Sébastien BrierMass Spectrometry for Biology Unit, Institut Pasteur, Paris, France.ORCID http://orcid.org/0000-0003-1758-8237
Reda AssalMolecular Mechanisms of Membrane Transport Laboratory, Institut Pasteur, Paris, France.
Juan Carlos Canul-TecMolecular Mechanisms of Membrane Transport Laboratory, Institut Pasteur, Paris, France.
Julia Chamot-RookeMass Spectrometry for Biology Unit, Institut Pasteur, Paris, France.
Nicolas ReyesMolecular Mechanisms of Membrane Transport Laboratory, Institut Pasteur, Paris, France.ORCID http://orcid.org/0000-0001-6618-8307
Centre National de la Recherche Scientifique · FR

Funding

Agence Nationale de la Recherche CACSICE grant ANR-11-EQPX-008Centre National de la Recherche Scientifique UMR 3528H2020 Excellent Science ERC Starting grant 309657
6 · The paper itself

Abstract

Human excitatory amino acid transporters (EAATs) take up the neurotransmitter glutamate in the brain and are essential to maintain excitatory neurotransmission. Our understanding of the EAATs' molecular mechanisms has been hampered by the lack of stability of purified protein samples for biophysical analyses. Here, we present approaches based on consensus mutagenesis to obtain thermostable EAAT1 variants that share up to ~95% amino acid identity with the wild type transporters, and remain natively folded and functional. Structural analyses of EAAT1 and the consensus designs using hydrogen-deuterium exchange linked to mass spectrometry show that small and highly cooperative unfolding events at the inter-subunit interface rate-limit their thermal denaturation, while the transport domain unfolds at a later stage in the unfolding pathway. Our findings provide structural insights into the kinetic stability of human glutamate transporters, and introduce general approaches to extend the lifetime of human membrane proteins for biophysical analyses.

Indexed as

Consensus SequenceTemperatureAmino Acid SequenceAmino Acid Transport System X-AGDeuterium Exchange MeasurementExcitatory Amino Acid Transporter 1HumansKineticsModels, MolecularMutant ProteinsNeurotransmitter AgentsProtein StabilityProtein SubunitsProtein UnfoldingAmino Acid Transport System X-AGExcitatory Amino Acid Transporter 1Mutant ProteinsNeurotransmitter AgentsProtein SubunitsSLC1A3 protein, humanbiochemistrychemical biologyconsensus amino acidhumanmolecular biophysicspermeation and transportprotein dynamicsprotein foldingprotein stabilitystructural biology

Identifiers

PMID30334738
PMCPMC6209432
OpenAlexW2896532438

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.