ArticleNature communications2022
Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Environmental Factors Drive Neurodegenerative Diseases Through Glutamate Excitotoxicity: A Convergent Mechanistic Pathway.Neuroscience bulletin · 2026Review
- Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.The EMBO journal · 2026Article
- Excitatory amino acid transporters support mast cell degranulation via α-KG-mediated methylation of Spp1.Cellular & molecular immunology · 2026Article
- MC-350013 and Corylin Emerge as Promising Neuroprotective Agents through Dual Targeting of xCT and GLT-1.Journal of molecular neuroscience : MN · 2026Article
- Novel insights of acupuncture in ischemic stroke: orchestrating neuro-endocrine-immune network.Frontiers in immunology · 2026Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- A systematic review on type 3 diabetes: bridging the gap between metabolic dysfunction and Alzheimer's disease.Diabetology & metabolic syndrome · 2025Review
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Structural basis of excitatory amino acid transporter 3 substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.EBioMedicine · 2025Article
- The development of a high-throughput acoustic droplet ejection mass-spectrometry assay and a solid-supported membrane (SSM)-based electrophysiological assay to study the pharmacological inhibition of SLC1-A3, -A2 and -A1 in a drug discovery program.Frontiers in pharmacology · 2025Article
- Inhibitory Potential of the Truncated Isoforms on Glutamate Transporter Oligomerization Identified by Computational Analysis of Gene-Centric Isoform Maps.Pharmaceutical research · 2024Article
- PS1/gamma-secretase acts as rogue chaperone of glutamate transporter EAAT2/GLT-1 in Alzheimer's disease.Acta neuropathologica communications · 2024Article
- Molecular Dynamic Simulations Reveal that Water-Soluble QTY-Variants of Glutamate Transporters EAA1, EAA2 and EAA3 Retain the Conformational Characteristics of Native Transporters.Pharmaceutical research · 2024Article
- Structural basis of the excitatory amino acid transporter 3 substrate recognition.bioRxiv : the preprint server for biology · 2024Article
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.Journal of respiratory biology and translational medicine · 2024Article
- Still in Search for an EAAT Activator: GT949 Does Not Activate EAAT2, nor EAAT3 in Impedance and Radioligand Uptake Assays.ACS chemical neuroscience · 2024Article
- Review
- The NERP-4-SNAT2 axis regulates pancreatic β-cell maintenance and function.Nature communications · 2023Article
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutamate is a pivotal excitatory neurotransmitter in mammalian brains, but excessive glutamate causes numerous neural disorders. Almost all extracellular glutamate is retrieved by the glial transporter, Excitatory Amino Acid Transporter 2 (EAAT2), belonging to the SLC1A family. However, in some cancers, EAAT2 expression is enhanced and causes resistance to therapies by metabolic disturbance. Despite its crucial roles, the detailed structural information about EAAT2 has not been available. Here, we report cryo-EM structures of human EAAT2 in substrate-free and selective inhibitor WAY213613-bound states at 3.2 Å and 2.8 Å, respectively. EAAT2 forms a trimer, with each protomer consisting of transport and scaffold domains. Along with a glutamate-binding site, the transport domain possesses a cavity that could be disrupted during the transport cycle. WAY213613 occupies both the glutamate-binding site and cavity of EAAT2 to interfere with its alternating access, where the sensitivity is defined by the inner environment of the cavity. We provide the characterization of the molecular features of EAAT2 and its selective inhibition mechanism that may facilitate structure-based drug design for EAAT2.
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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.