ArticleThe Journal of biological chemistry2012
Identification of in vivo disulfide conformation of TRPA1 ion channel.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Article
- Novel Compounds for Hair Repair: Chemical Characterization and In Vitro Analysis of Thiol Cross-Linking Agents.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis.Molecules (Basel, Switzerland) · 2024Review
- Hydrogen Sulfide (HBiomolecules · 2024Review
- Intramolecular Disulfide Bonds for Biogenesis of CALHM1 Ion Channel Are Dispensable for Voltage-Dependent ActivationMolecules and cells · 2021Article
- TRP Channels as Sensors of Aldehyde and Oxidative Stress.Biomolecules · 2021Review
- Hydrogen Sulfide (HBiomolecules · 2021Review
- Hydrogen sulfide signalling in the CNS - Comparison with NO.British journal of pharmacology · 2020Review
- Electrophile-Induced Conformational Switch of the Human TRPA1 Ion Channel Detected by Mass Spectrometry.International journal of molecular sciences · 2020Article
- Signalling by hydrogen sulfide and polysulfides via protein S-sulfuration.British journal of pharmacology · 2020Review
- Regulation of vascular tone by transient receptor potential ankyrin 1 channels.Current topics in membranes · 2020Review
- To flourish or perish: evolutionary TRiPs into the sensory biology of plant-herbivore interactions.Pflugers Archiv : European journal of physiology · 2019Review
- Review
- Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition.The Journal of general physiology · 2018Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Structural basis of ligand interaction with atypical chemokine receptor 3.Nature communications · 2017Article
- Capsaicin-Sensitive Sensory Nerves Mediate the Cellular and Microvascular Effects of H2S via TRPA1 Receptor Activation and Neuropeptide Release.Journal of molecular neuroscience : MN · 2016Article
- Role of reactive oxygen species and TRP channels in the cough reflex.Cell calcium · 2016Review
- N-terminal tetrapeptide T/SPLH motifs contribute to multimodal activation of human TRPA1 channel.Scientific reports · 2016Article
- The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1.The Journal of general physiology · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
TRPA1 (transient receptor potential ankyrin 1) is an ion channel expressed in the termini of sensory neurons and is activated in response to a broad array of noxious exogenous and endogenous thiol-reactive compounds, making it a crucial player in chemical nociception. A number of conserved cysteine residues on the N-terminal domain of the channel have been identified as critical for sensing these electrophilic pungent chemicals, and our recent EM structure with modeled domains predicts that these cysteines form a ligand-binding pocket, allowing for the possibility of disulfide bonding between the cysteine residues. Here, we present a comprehensive mass spectrometry investigation of the in vivo disulfide bonding conformation and in vitro reactivity of 30 of the 31 cysteine residues in the TRPA1 ion channel. Four disulfide bonds were detected in the in vivo TRPA1 structure: Cys-666-Cys-622, Cys-666-Cys-463, Cys-622-Cys-609, and Cys-666-Cys-193. All of the cysteines detected were reactive to N-methylmaleimide (NMM) in vitro, with varying degrees of labeling efficiency. Comparison of the ratio of the labeling efficiency at 300 μM versus 2 mM NMM identified a number of cysteine residues that were outliers from the mean labeling ratio, suggesting that protein conformation changes rendered these cysteines either more or less protected from labeling at the higher NMM concentrations. These results indicate that the activation mechanism of TRPA1 may involve N-terminal conformation changes and disulfide bonding between critical cysteine residues.
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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.