ArticleeLife2016
Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- Review
- Ion Channel-Targeting Toxins: Structural Mechanisms of Activation, Inhibition, and Therapeutic Potential.Toxins · 2025Review
- Neurotoxins Acting on TRPV1-Building a Molecular Template for the Study of Pain and Thermal Dysfunctions.Toxins · 2025Review
- Article
- Genetic code expansion, click chemistry, and light-activated PI3K reveal details of membrane protein trafficking downstream of receptor tyrosine kinases.bioRxiv : the preprint server for biology · 2024Article
- Identification and Evolutionary Analysis of the Widely Distributed CAP Superfamily in Spider Venom.Toxins · 2024Article
- Dual receptor-sites reveal the structural basis for hyperactivation of sodium channels by poison-dart toxin batrachotoxin.Nature communications · 2024Article
- Structural Basis of the Bivalency of the TRPV1 Agonist DkTx.Angewandte Chemie (International ed. in English) · 2024Article
- Dissecting the contributions of membrane affinity and bivalency of the spider venom protein DkTx to its sustained mode of TRPV1 activation.The Journal of biological chemistry · 2023Article
- ScrepYard: An online resource for disulfide-stabilized tandem repeat peptides.Protein science : a publication of the Protein Society · 2023Article
- A journey from molecule to physiology andFrontiers in pharmacology · 2023Review
- TRP channels: a journey towards a molecular understanding of pain.Nature reviews. Neuroscience · 2022Review
- Sensory TRP Channels in Three Dimensions.Annual review of biochemistry · 2022Review
- Molecular determinants of inhibition of the human proton channel hHv1 by the designer peptide C6 and a bivalent derivative.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis.Nature communications · 2022Article
- Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.International journal of molecular sciences · 2022Review
- Targeting Lipid-Ion Channel Interactions in Cardiovascular Disease.Frontiers in cardiovascular medicine · 2022Article
- Evaluation of Efficient Non-reducing Enzymatic and Chemical Ligation Strategies for Complex Disulfide-Rich Peptides.Bioconjugate chemistry · 2021Article
- Heat-dependent opening of TRPV1 in the presence of capsaicin.Nature structural & molecular biology · 2021Article
- Deficiency of Inositol Monophosphatase Activity Decreases Phosphoinositide Lipids and Enhances TRPV1 FunctionThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation.
Indexed as
Identifiers
What OpenQuestion holds
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.