2023
Molecular mechanism of hyperactivation conferred by a truncation of TRPA1
Bali A, Schaefer S, Trier I, Zhang A, Kabeche L, Paulsen C. Molecular mechanism of hyperactivation conferred by a truncation of TRPA1. Nature Communications 2023, 14: 2867. PMID: 37208332, PMCID: PMC10199097, DOI: 10.1038/s41467-023-38542-1.Peer-Reviewed Original ResearchConceptsChannel sensitizationPlasma membraneHeterologous cellsGenetic analysisMolecular mechanismsBiochemical assaysHeteromeric channelsNonsense mutationPhysiological impactMutantsAgonist sensitivityCalcium permeabilityEnergetic barrierSubunitsTRPA1MutationsTractable mechanismMechanismHyperactivationMembraneCellsActivationAssaysGatingTruncation
2020
Irritant-evoked activation and calcium modulation of the TRPA1 receptor
Zhao J, Lin King JV, Paulsen CE, Cheng Y, Julius D. Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 2020, 585: 141-145. PMID: 32641835, PMCID: PMC7483980, DOI: 10.1038/s41586-020-2480-9.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCalciumCysteineElectric ConductivityHumansIodoacetamideIon Channel GatingModels, MolecularMutationOximesTRPA1 Cation ChannelConceptsPrimary afferent nerve fibersTRP channel subtypesAfferent nerve fibersIon channel TRPA1Inflammatory painIrritant receptorsMetabotropic receptorsTRPA1 receptorsCytoplasmic second messengersNerve fibersChannel subtypesCalcium permeabilityCalcium modulationTRPA1 regulationTRPA1Environmental toxicantsFunctional couplingReceptorsPainItchExogenous agentsAttractive targetIrritantsActivationSecond messenger
2015
Structure of the TRPA1 ion channel suggests regulatory mechanisms
Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D. Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 2015, 520: 511-517. PMID: 25855297, PMCID: PMC4409540, DOI: 10.1038/nature14367.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnalgesicsAnkyrin RepeatAnti-Inflammatory AgentsBinding SitesCalcium ChannelsCryoelectron MicroscopyCytosolHumansModels, MolecularNerve Tissue ProteinsPolyphosphatesProtein StabilityProtein SubunitsStructure-Activity RelationshipTransient Receptor Potential ChannelsTRPA1 Cation ChannelConceptsTRPA1 ion channelsCoil assembly domainIon channelsCovalent protein modificationSingle-particle electronAnti-inflammatory agentsTransient receptor potentialStructure-based designAllosteric domainProtein modificationRegulatory mechanismsChannel regulationNoxious chemical agentsTRPA1 regulationAssembly domainIrritant exposureTRPA1 antagonistInflammatory conditionsTissue injuryTRPA1 functionStructural mechanismsDrug metabolismPotent antagonistReceptor potentialHuman TRPA1