ArticleNature communications2023
Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Stabilized adaptive states in microbiome-human integrated physiology: reframing health and chronic disease as symbiotic biological states.Frontiers in medicine · 2026Pooled it
- Large-scale multi-trait genome-wide analysis for inflammatory bowel disease reveals new insights into its molecular mechanisms and emphasizes the roles of systemic immune regulation.Briefings in bioinformatics · 2025Pooled it
- The SLC15A4-TASL complex is essential for lupus development in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Pharmacology of the SLC15A4-TASL Complex, an Emerging Target for the Treatment of Lupus.Pharmacology research & perspectives · 2026Review
- Structural basis for multivitamin recognition and transport by human SMVT.Nature communications · 2026Article
- Membrane-decisional architecture: a framework for multigenomic signal prioritization in the plasma membrane nanobiome.Frontiers in physiology · 2026Review
- mRNA Cancer Vaccines: From Pandemic Paradigm to Personalized Oncology Therapeutics.Cancer innovation · 2025Review
- Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.The Journal of clinical investigation · 2025Article
- METTL3/ALKBH5-Mediated N6-Methyladenosine Modification Drives Macrophage M1 Polarization via the SLC15A3-TASL-IRF5 Signaling Axis in Psoriasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TLR-induced STK25 activation promotes IRF5-mediated inflammation.Life science alliance · 2025Article
- Development of conformation-selective antibodies targeting human SLC15A4.Nature communications · 2025Article
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- CCDC134 controls TLR biogenesis through the ER chaperone Gp96.The Journal of experimental medicine · 2025Article
- The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.Nature communications · 2025Article
- Unidirectional and bidirectional causation between smoking and blood DNA methylation: evidence from twin-based Mendelian randomisation.European journal of epidemiology · 2025Article
- Cytosolic delivery of innate immune agonists.Trends in immunology · 2024Review
- New approaches to the control of chronic inflammatory diseases with a focus on the endolysosomal system of immune cells.International immunology · 2024Review
- Unidirectional and Bidirectional Causation between Smoking and Blood DNA Methylation: Evidence from Twin-based Mendelian Randomisation.medRxiv : the preprint server for health sciences · 2024Article
- The Role of ABCB1, ABCG2, and SLC Transporters in Pharmacokinetic Parameters of Selected Drugs and Their Involvement in Drug-Drug Interactions.Membranes · 2024Review
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.
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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.