ArticleNature structural & molecular biology2017
Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Article
- Discovery of Two Novel Scorpion Venom Peptides Activating TRPML2 to Impair ZIKV Internalization.Toxins · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Somatic Mutations inHypertension (Dallas, Tex. : 1979) · 2025Article
- TRPML2 in distinct states reveals the activation and modulation principles of the TRPML family.Nature communications · 2025Article
- Forty sites of TRP channel regulation.Current opinion in chemical biology · 2025Review
- Disease-associated missense mutations in the pore loop of polycystin-2 alter its ion channel function in a heterologous expression system.The Journal of biological chemistry · 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
- Bidirectional Allosteric Coupling between PIPInternational journal of molecular sciences · 2024Article
- TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.Biomolecules · 2023Review
- TRPML3/BK complex promotes autophagy and bacterial clearance by providing a positive feedback regulation of mTOR via PI3P.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A Structural Overview of TRPML1 and the TRPML Family.Handbook of experimental pharmacology · 2023Article
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- 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
- Ligand-Binding Sites in Vanilloid-Subtype TRP Channels.Frontiers in pharmacology · 2022Review
- Review
- Atomic insights into ML-SI3 mediated human TRPML1 inhibition.Structure (London, England : 1993) · 2021Article
- Structural Pharmacology of TRP Channels.Journal of molecular biology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
TRPML3 channels are mainly localized to endolysosomes and play a critical role in the endocytic pathway. Their dysfunction causes deafness and pigmentation defects in mice. TRPML3 activity is inhibited by low endolysosomal pH. Here we present cryo-electron microscopy (cryo-EM) structures of human TRPML3 in the closed, agonist-activated, and low-pH-inhibited states, with resolutions of 4.06, 3.62, and 4.65 Å, respectively. The agonist ML-SA1 lodges between S5 and S6 and opens an S6 gate. A polycystin-mucolipin domain (PMD) forms a luminal cap. S1 extends into this cap, forming a 'gating rod' that connects directly to a luminal pore loop, which undergoes dramatic conformational changes in response to low pH. S2 extends intracellularly and interacts with several intracellular regions to form a 'gating knob'. These unique structural features, combined with the results of electrophysiological studies, indicate a new mechanism by which luminal pH and other physiological modulators such as PIP
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