ArticleeLife2019
Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.
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.
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- Glutamine Metabolism in Health and Diseases.MedComm · 2026Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- ESMDynamic: Fast and accurate prediction of protein dynamic contact maps from single sequences.Nature communications · 2026Article
- Integrative Omics Reveals Glutamine Catabolism-Driven Apoptotic Suppression in Monocytes upon Mechanical Unloading.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Recent advances in ASCT2 inhibitors: ligand design and therapeutic applications.Future medicinal chemistry · 2025Review
- Article
- Structural basis of excitatory amino acid transporter 3 substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alternative splicing: hallmark and therapeutic opportunity in metabolic liver disease.Gastroenterology report · 2025Review
- KLF7 Promotes Hepatocellular Carcinoma Progression Through Regulating SLC1A5-Mediated Tryptophan Metabolism.Journal of cellular and molecular medicine · 2024Article
- 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 · 2024Article
- Structural basis of the excitatory amino acid transporter 3 substrate recognition.bioRxiv : the preprint server for biology · 2024Article
- ASCT2 is a major contributor to serine uptake in cancer cells.Cell reports · 2024Article
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Discovery and Synthesis of Hydroxy-l-Proline Blockers of the Neutral Amino Acid Transporters SLC1A4 (ASCT1) and SLC1A5 (ASCT2).Molecules (Basel, Switzerland) · 2024Article
- On the substrate turnover rate of NBCe1 and AE1 SLC4 transporters: structure-function considerations.Frontiers in physiology · 2024Article
- ASCT2 is the primary serine transporter in cancer cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- Glutaminolysis and peripheral CD4Frontiers in immunology · 2023Review
- Cryo-EM structures of pentameric autoinducer-2 exporter from Escherichia coli reveal its transport mechanism.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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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.