ArticleComputational and structural biotechnology journal2021
A structural view onto disease-linked mutations in the human neutral amino acid exchanger ASCT1.
Article in Computational and structural biotechnology journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 17 citations in OpenAlex.
- Case Report of Dual Variants inClinical case reports · 2026Article
- Structural basis of excitatory amino acid transporter 3 substrate recognition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A new type of blood-brain barrier aminoacidopathy underlies metabolic microcephaly associated with SLC1A4 mutations.Brain : a journal of neurology · 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
- Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.Annals of clinical and translational neurology · 2023Article
- Novel compound heterozygous variants (c.971delA/c.542C > T) inFrontiers in pediatrics · 2023Article
- Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2.Nature communications · 2022Article
- Structural basis of ligand binding modes of human EAAT2.Nature communications · 2022Article
- Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives.International journal of molecular sciences · 2022Review
- Synergistic Control of Transmitter Turnover at Glycinergic Synapses by GlyT1, GlyT2, and ASC-1.International journal of molecular sciences · 2022Review
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ASCT1 transporter of the SLC1 family is largely involved in equilibration of neutral amino acids' pools across the plasma membrane and plays a prominent role in the transport of both L- and D-isomers of serine, essential for the normal functioning of the central nervous system in mammals. A number of mutations in ASCT1 (E256K, G381R, R457W) have been linked to severe neurodevelopmental disorders, however in the absence of ASCT1 structure it is hard to understand their impact on substrate transport. To ameliorate that we have determined a cryo-EM structure of human ASCT1 at 4.2 Å resolution and performed functional transport assays and molecular dynamics simulations, which revealed that given mutations lead to the diminished transport capability of ASCT1 caused by instability of transporter and impeded transport cycle.
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