ArticleStructure (London, England : 1993)2021
Atomic insights into ML-SI3 mediated human TRPML1 inhibition.
Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Lysosomal zinc nanomodulation blocks macrophage pyroptosis for counteracting atherosclerosis progression.Science advances · 2025Article
- TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.Nature communications · 2025Article
- Hyperosmotic Stress Promotes the Nuclear Translocation of TFEB in Tubular Epithelial Cells Depending on Intracellular CaCellular and molecular bioengineering · 2025Article
- INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.The Journal of cell biology · 2024Article
- Lysosomal CaScientific reports · 2024Article
- Article
- TRPML1 gating modulation by allosteric mutations and lipids.bioRxiv : the preprint server for biology · 2024Article
- Activation of the TRPML1 Ion Channel Induces Proton Secretion in the Human Gastric Parietal Cell Line HGT-1.International journal of molecular sciences · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Molecular and structural basis of the dual regulation of the polycystin-2 ion channel by small-molecule ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain.Neuroscience insights · 2023Review
- Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms.Frontiers in molecular neuroscience · 2023Review
- Structural mechanism of allosteric activation of TRPML1 by PI(3,5)PProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Ligand-Binding Sites in Vanilloid-Subtype TRP Channels.Frontiers in pharmacology · 2022Review
- Lysosomal ZnCell reports · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Transient receptor potential mucolipin 1 (TRPML1) regulates lysosomal calcium signaling, lipid trafficking, and autophagy-related processes. This channel is regulated by phosphoinositides and the low pH environment of the lysosome, maintaining calcium levels essential for proper lysosomal function. Recently, several small molecules specifically targeting the TRPML family have been demonstrated to modulate channel activity. One of these, a synthetic antagonist ML-SI3, can prevent lysosomal calcium efflux and has been reported to block downstream TRPML1-mediated induction of autophagy. Here, we report a cryo-electron microscopy structure of human TRPML1 with ML-SI3 at 2.9-Å resolution. ML-SI3 binds to the hydrophobic cavity created by S5, S6, and PH1, the same cavity where the synthetic agonist ML-SA1 binds. Electrophysiological characterizations show that ML-SI3 can compete with ML-SA1, blocking channel activation yet does not inhibit PI(3,5)P
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Registered trials
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.