The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Structure of the TRPA1 ion channel suggests regulatory mechanisms
Open accessAbstract
The TRPA1 ion channel (also known as the wasabi receptor) is a detector of noxious chemical agents encountered in our environment or produced endogenously during tissue injury or drug metabolism. These include a broad class of electrophiles that activate the channel through covalent protein modification. TRPA1 antagonists hold potential for treating neurogenic inflammatory conditions provoked or exacerbated by irritant exposure. Despite compelling reasons to understand TRPA1 function, structural mechanisms underlying channel regulation remain obscure. Here we use single-particle electron cryo- microscopy to determine the structure of full-length human TRPA1 to ∼4 Å resolution in the presence of pharmacophores, including a potent antagonist. Several unexpected features are revealed, including an extensive coiled-coil assembly domain stabilized by polyphosphate co-factors and a highly integrated nexus that converges on an unpredicted transient receptor potential (TRP)-like allosteric domain. These findings provide new insights into the mechanisms of TRPA1 regulation, and establish a blueprint for structure-based design of analgesic and anti-inflammatory agents.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
Overview of the CCP 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353
RELION: Implementation of a Bayesian approach to cryo-EM structure determination
Scheres, S. H. W. (2012) · Journal of Structural Biology · doi:10.1016/j.jsb.2012.09.006 · Cited by 5,446
The Design of Coiled-Coil Structures and Assemblies
Woolfson, D. N. (2005) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(05)70004-8 · Cited by 585
Cited by
Hayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654
TRPA1 channels: molecular sentinels of cellular stress and tissue damage
Viana, F. (2016) · The Journal of Physiology · doi:10.1113/jp270935 · Cited by 210
MLKL Requires the Inositol Phosphate Code to Execute Necroptosis
Dovey, C. M., Diep, J., Clarke, B. P., Hale, A. T., McNamara, D. E., Guo, H., Brown, N. W., Cao, J. Y., Grace, C. R., Gough, P. J., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.010 · Cited by 175
Elephantid Genomes Reveal the Molecular Bases of Woolly Mammoth Adaptations to the Arctic
Lynch, V. J., Bedoya-Reina, O. C., Ratan, A., Sulak, M., Drautz-Moses, D. I., Perry, G. H., Miller, W., & Schuster, S. C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.027 · Cited by 130
Suchyna, T. M. (2017) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2017.07.011 · Cited by 111
Biomimetic temperature-sensing layer for artificial skins
Di Giacomo, R., Bonanomi, L., Costanza, V., Maresca, B., & Daraio, C. (2017) · Science Robotics · doi:10.1126/scirobotics.aai9251 · Cited by 88
The Inositol Phosphate Signalling Network in Physiology and Disease
Kim, S., Bhandari, R., Brearley, C. A., & Saiardi, A. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.08.005 · Cited by 70
TRPA1 rare variants in chronic neuropathic and nociplastic pain patients
Marchi, M., Salvi, E., Andelic, M., Mehmeti, E., D'Amato, I., Cazzato, D., Chiappori, F., Lombardi, R., Cartelli, D., Devigili, G., et al. (2023) · Pain · doi:10.1097/j.pain.0000000000002905 · Cited by 29
TRPA1 promotes melanosome phagocytosis in keratinocytes via PAR-2/CYLD axis
Wang, Y., Li, Z., Wu, W., Liu, Y., Xiao, Y., Qi, D., Zhao, G., Zhou, M., Wang, H., Liu, J., et al. (2022) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2022.05.005 · Cited by 12
Zhang, H., Zheng, D., Wu, Q., Yan, N., Peng, H., Hu, Q., Peng, Y., Yan, Z., Shi, Z., Bao, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59797-w · Cited by 12
Mao, R., & Li, J. (2024) · BMC Medical Genomics · doi:10.1186/s12920-024-02008-0 · Cited by 5
Metadata
- Authors
- Paulsen, C. E., Armache, J.-P., Gao, Y., Cheng, Y., & Julius, D.
- Venue
- Nature
- Published
- 2015-04-08
- Volume
- 520
- Issue
- 7548
- Pages
- 511-517
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1984533345
- Cited by
- 660
- References
- 5
- FWCI
- 54.45
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
