ArticleProceedings of the National Academy of Sciences of the United States of America2021
Structural basis for substrate specificity of heteromeric transporters of neutral amino acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Structures of the neutral amino acid transporter LAT4 provide insights into antitumor effects of its inhibitor tubeimoside-1.The EMBO journal · 2026Article
- Structural insights into a conserved mechanism of choline translocation through CHT.Science advances · 2026Article
- Lens tissue transcriptome analysis in patients with total congenital cataract.Human genomics · 2026Article
- Characterization of the YCjN ABC Transporter in Escherichia coli: Role in Maltose and Ethidium Bromide Transport.Molecular biotechnology · 2026Article
- Oncogenic role of the SLC7A13-SLC3A1 cystine transporter in human luminal breast cancer and its cryo-EM structure.Protein & cell · 2026Article
- Structural insights into cationic amino acid transport and viral receptor engagement by CAT1.Nature communications · 2025Article
- Manganese homeostasis modulates glucan and chitin unmasking in the opportunistic yeastVirulence · 2025Article
- Abnormal β-Hydroxybutyrylation Modification of ARG1 Drives Reprogramming of Arginine Metabolism to Promote the Progression of Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- Structural basis for the substrate recognition and transport mechanism of the human yScience advances · 2025Article
- Review
- Structural basis of anticancer drug recognition and amino acid transport by LAT1.Nature communications · 2025Article
- The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.PNAS nexus · 2025Article
- GCN2-SLC7A11 axis coordinates autophagy, cell cycle and apoptosis and regulates cell growth in retinoblastoma upon arginine deprivation.Cancer & metabolism · 2024Article
- Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.Nature communications · 2024Article
- Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study.International journal of molecular sciences · 2023Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- The Role of Solute Carrier Transporters in Efficient Anticancer Drug Delivery and Therapy.Pharmaceutics · 2023Review
- CD98 heavy chain as a prognostic biomarker and target for cancer treatment.Frontiers in oncology · 2023Review
- Structure of the human heterodimeric transporter 4F2hc-LAT2 in complex with Anticalin, an alternative binding protein for applications in single-particle cryo-EM.Scientific reports · 2022Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Despite having similar structures, each member of the heteromeric amino acid transporter (HAT) family shows exquisite preference for the exchange of certain amino acids. Substrate specificity determines the physiological function of each HAT and their role in human diseases. However, HAT transport preference for some amino acids over others is not yet fully understood. Using cryo-electron microscopy of apo human LAT2/CD98hc and a multidisciplinary approach, we elucidate key molecular determinants governing neutral amino acid specificity in HATs. A few residues in the substrate-binding pocket determine substrate preference. Here, we describe mutations that interconvert the substrate profiles of LAT2/CD98hc, LAT1/CD98hc, and Asc1/CD98hc. In addition, a region far from the substrate-binding pocket critically influences the conformation of the substrate-binding site and substrate preference. This region accumulates mutations that alter substrate specificity and cause hearing loss and cataracts. Here, we uncover molecular mechanisms governing substrate specificity within the HAT family of neutral amino acid transporters and provide the structural bases for mutations in LAT2/CD98hc that alter substrate specificity and that are associated with several pathologies.
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