Evidence map›Paper›PMID 33658209›Full record

ArticleScience advances2021

Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.

Biao Qiu, Doreen Matthies, Eva Fortea, Zhiheng Yu, Olga Boudker

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

36 citing papers in PubMed, 45 citations in OpenAlex.

  1. Multimodal dynamics control activity of a glial glutamate transporter.bioRxiv : the preprint server for biology · 2026
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  5. Structural basis of excitatory amino acid transporter 3 substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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 1 country.

Biao QiuDepartment of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, USA.ORCID 0000-0003-3633-5091
Doreen MatthiesHoward Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.ORCID 0000-0001-9221-4484
Eva ForteaDepartment of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, USA.
Zhiheng YuHoward Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.ORCID 0000-0002-7114-2570
Olga BoudkerDepartment of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Ave, New York, NY 10021, USA. olb2003@med.cornell.edu.ORCID 0000-0001-6965-0851
Howard Hughes Medical Institute · USCornell University · US

Funding

Towards high-resolution structural biology of membrane protein complexes in their native lipid environmentZIAHD008998 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MATTHIES, DOREEN · 2021 to 2025
$10.7M
The structural dynamics of a glutamate transporter homologueR37NS085318 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BOUDKER, OLGA · 2014 to 2020
$4.3M
Conformational Ensemble of Glutamate Transporters: Structure and IonicModulationR01NS064357 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BOUDKER, OLGA · 2009 to 2018
$3.8M
NINDS NIH HHS R01 NS064357NINDS NIH HHS R37 NS085318
6 · The paper itself

Abstract

Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which a conserved glutamate residue mediates proton symport.

Indexed as

ProtonsBinding SitesCryoelectron MicroscopyExcitatory Amino Acid Transporter 3Glutamic AcidHumansIonsSodiumExcitatory Amino Acid Transporter 3Glutamic AcidIonsProtonsSLC1A1 protein, humanSodium

Identifiers

PMID33658209
PMCPMC7929514
OpenAlexW3134446085

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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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.