ArticleProceedings of the National Academy of Sciences of the United States of America2016
Rational design and validation of a vanilloid-sensitive TRPV2 ion channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Perspectives on TRPV Channels in the Structural and Computational Revolution Era.Advances in experimental medicine and biology · 2026Review
- Molecular determinants of 2-aminoethoxydiphenyl borate sensitivity of transient receptor potential vanilloid 2-unexpected differences between 2 rodent orthologs.Molecular pharmacology · 2025Article
- TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.Molecular neurobiology · 2025Review
- Article
- Conservation of the cooling agent binding pocket within the TRPM subfamily.bioRxiv : the preprint server for biology · 2024Article
- Non-canonical helical transitions and conformational switching are associated with characteristic flexibility and disorder indices in TRP and Kv channels.Channels (Austin, Tex.) · 2023Article
- Improvement of wound healing by capsaicin through suppression of the inflammatory response and amelioration of the repair process.Molecular medicine reports · 2023Article
- Capsaicin Changes the Pattern of Brain Rhythms in Sleeping Rats.Molecules (Basel, Switzerland) · 2023Article
- Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1.International journal of molecular sciences · 2023Article
- Article
- Cannabidiol sensitizes TRPV2 channels to activation by 2-APB.bioRxiv : the preprint server for biology · 2023Article
- Transient Receptor Potential Channels: Important Players in Ocular Pain and Dry Eye Disease.Pharmaceutics · 2022Review
- Structural basis for promiscuous action of monoterpenes on TRP channels.Communications biology · 2021Article
- Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy.Pharmaceutics · 2021Review
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Article
- Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.Trends in biochemical sciences · 2020Review
- Molecular mechanisms underlying menthol binding and activation of TRPM8 ion channel.Nature communications · 2020Article
- High-resolution structures of transient receptor potential vanilloid channels: Unveiling a functionally diverse group of ion channels.Protein science : a publication of the Protein Society · 2020Review
- Gating of human TRPV3 in a lipid bilayer.Nature structural & molecular biology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Vanilloids activation of TRPV1 represents an excellent model system of ligand-gated ion channels. Recent studies using cryo-electron microcopy (cryo-EM), computational analysis, and functional quantification revealed the location of capsaicin-binding site and critical residues mediating ligand-binding and channel activation. Based on these new findings, here we have successfully introduced high-affinity binding of capsaicin and resiniferatoxin to the vanilloid-insensitive TRPV2 channel, using a rationally designed minimal set of four point mutations (F467S-S498F-L505T-Q525E, termed TRPV2_Quad). We found that binding of resiniferatoxin activates TRPV2_Quad but the ligand-induced open state is relatively unstable, whereas binding of capsaicin to TRPV2_Quad antagonizes resiniferatoxin-induced activation likely through competition for the same binding sites. Using Rosetta-based molecular docking, we observed a common structural mechanism underlying vanilloids activation of TRPV1 and TRPV2_Quad, where the ligand serves as molecular "glue" that bridges the S4-S5 linker to the S1-S4 domain to open these channels. Our analysis revealed that capsaicin failed to activate TRPV2_Quad likely due to structural constraints preventing such bridge formation. These results not only validate our current working model for capsaicin activation of TRPV1 but also should help guide the design of drug candidate compounds for this important pain sensor.
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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.