Evidence map›Paper›PMID 31580259›Full record

ArticleeLife2019

Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.

Xiaodi Yu, Olga Plotnikova, Paul D Bonin, Timothy A Subashi, Thomas J McLellan, Darren Dumlao, Ye Che, Yin Yao Dong, Elisabeth P Carpenter, Graham M West and 3 more

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 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 76 citations in OpenAlex.

  1. Review
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  8. Structural basis of excitatory amino acid transporter 3 substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
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  11. Receptor usage of Syncytin-1: ASCT2, but not ASCT1, is a functional receptor and effector of cell fusion in the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Article
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  15. Article
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  17. ASCT2 is the primary serine transporter in cancer cells.bioRxiv : the preprint server for biology · 2023
    Article
  18. Article
  19. Glutaminolysis and peripheral CD4Frontiers in immunology · 2023
    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

13 authors at 2 institutions in 2 countries.

Xiaodi Yu *Medicine Design, Pfizer Inc, Groton, United States.
Olga Plotnikova *Medicine Design, Pfizer Inc, Groton, United States.
Paul D BoninMedicine Design, Pfizer Inc, Groton, United States.
Timothy A SubashiMedicine Design, Pfizer Inc, Groton, United States.
Thomas J McLellanMedicine Design, Pfizer Inc, Groton, United States.
Darren DumlaoMedicine Design, Pfizer Inc, Groton, United States.
Ye CheMedicine Design, Pfizer Inc, Groton, United States.
Yin Yao DongStructural Genomics Consortium, University of Oxford, Oxford, United Kingdom.
Elisabeth P CarpenterStructural Genomics Consortium, University of Oxford, Oxford, United Kingdom.
Graham M WestMedicine Design, Pfizer Inc, Groton, United States.
Xiayang QiuMedicine Design, Pfizer Inc, Groton, United States.
Jeffrey S CulpMedicine Design, Pfizer Inc, Groton, United States.
Seungil HanMedicine Design, Pfizer Inc, Groton, United States.ORCID 0000-0002-1070-3880
Pfizer (United States) · USUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation. These structures reveal insights into the conformation of the critical ECL2a loop which connects the two domains, thus allowing rigid body movement of the transport domain throughout the transport cycle. Furthermore, the structures provide new insights into substrate recognition, which involves conformational changes in the HP2 loop. A putative cholesterol binding site was observed near the domain interface in the outward-facing state. Comparison with the previously determined inward-facing structure of SCL1A5 provides a basis for a more integrated understanding of substrate recognition and transport mechanism in the SLC1 family.

Indexed as

Amino Acid Transport System ASCCryoelectron MicroscopyGlutamineHumansMinor Histocompatibility AntigensProtein BindingProtein ConformationAmino Acid Transport System ASCGlutamineMinor Histocompatibility AntigensSLC1A5 protein, humanASCT2cryo-EMglutamine transporterhumanmolecular biophysicsoutward-facing conformationSLC1A5solute carrierstructural biology

Identifiers

PMID31580259
PMCPMC6800002
OpenAlexW2978816652

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.