ArticleeLife2021
Structural basis for human TRPC5 channel inhibition by two distinct inhibitors.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- Transient receptor potential canonical (TRPC) channels in diabetes and associated complications.Channels (Austin, Tex.) · 2026Review
- Comparative Ion Channel Transcriptomes of NK1R and Somatostatin Neurons in the PreBötzinger Complex of the Ventrolateral Medulla.Molecular neurobiology · 2026Article
- Comparative Ion Channel Transcriptomes of NK1R and Somatostatin Neurons in the preBötzinger Complex of the Ventrolateral Medulla.Research square · 2026Article
- Cryo-EM Structure of the TRPC1/5 Heteromer Enables Design of Antidepressant and Anxiolytic Drug with Reduced Side Effects.Nature communications · 2026Article
- (-)-Englerin A binding to human TRPC5 exposes an aromatic interaction network in channel activation.Nature communications · 2026Article
- Structural mechanism of substrate binding and inhibition of human taurine transporter.Nature communications · 2026Article
- Ideal efficacy photoswitching for chromocontrol of TRPC4/5 channel functions in live tissues.Nature chemical biology · 2026Article
- TRPV2 and TRPC5 are potential targets for astringent phytochemicals.Current research in food science · 2026Article
- Structure-guided design of picomolar-level macrocyclic TRPC5 channel inhibitors with antidepressant activity.Acta pharmaceutica Sinica. B · 2026Article
- Drug Discovery Applications of Nitroso (Hetero)Arene Derivatives.ChemPlusChem · 2025Review
- Molecular architecture of the human TRPC1/C5 heteromeric channel.Nature communications · 2025Article
- Impact of C-Terminal PKC Phosphorylation on TRPC6 Current Kinetics.International journal of molecular sciences · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Structural mechanism of the agonist binding on human TRPC3 channel.Nature communications · 2025Article
- Mechanism of (-)-Englerin A and calcium binding on the human TRPC5 channel.Protein science : a publication of the Protein Society · 2025Article
- Tricyclic antidepressants dose-dependently modulate the biphasic activity of the TRPC5 channel through opioid receptors.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Structural and accessibility studies highlight the differential binding of clemizole to TRPC5 and TRPC6.Journal of biomolecular structure & dynamics · 2025Article
- Molecular basis of neurosteroid and anticonvulsant regulation of TRPM3.Nature structural & molecular biology · 2025Article
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
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Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Here, we present the cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. The structures reveal that clemizole binds inside the voltage sensor-like domain of each subunit. In contrast, HC-070 is wedged between adjacent subunits and replaces the glycerol group of a putative diacylglycerol molecule near the extracellular side. Moreover, we found mutations in the inhibitor binding pockets altered the potency of inhibitors. These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a nonconductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5.
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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.