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
2022
Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1
Skoko J, Cao J, Gaboriau D, Attar M, Asan A, Hong L, Paulsen C, Ma H, Liu Y, Wu H, Harkness T, Furdui C, Manevich Y, Morrison C, Brown E, Normolle D, Spies M, Spies M, Carroll K, Neumann C. Redox regulation of RAD51 Cys319 and homologous recombination by peroxiredoxin 1. Redox Biology 2022, 56: 102443. PMID: 36058112, PMCID: PMC9450138, DOI: 10.1016/j.redox.2022.102443.Peer-Reviewed Original ResearchConceptsRAD51 foci formationFoci formationRedox regulationHomologous recombination DNA repair pathwayHR DNA repairProtein binding partnersPoly (ADP-ribose) polymeraseDNA repair pathwaysDAz-2Rad51 proteinSensitization of cellsRad51 filamentsBinding partnerHomologous recombinationDNA repairCysteine oxidationRepair pathwaysMediator proteinsHuman breast cancer cellsCellular responsesPeroxiredoxin 1Breast cancer cellsDNA damagePRDX1Cys319
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 ResearchConceptsPrimary 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
2017
A Gate Hinge Controls the Epithelial Calcium Channel TRPV5
van der Wijst J, Leunissen EH, Blanchard MG, Venselaar H, Verkaart S, Paulsen CE, Bindels RJ, Hoenderop JG. A Gate Hinge Controls the Epithelial Calcium Channel TRPV5. Scientific Reports 2017, 7: 45489. PMID: 28374795, PMCID: PMC5379628, DOI: 10.1038/srep45489.Peer-Reviewed Original ResearchConceptsEpithelial calcium channel TRPV5Detailed molecular insightStructure-function analysisSite-directed mutagenesisChannel gating mechanismCalcium channel TRPV5TRP channel familyCarboxy terminusDepth structure-function analysisFunctional crosstalkGlycine residueHomology modelingMolecular insightsChannel familyCell deathPermeation pathwayChannel functionChannel TRPV5Increased cell deathNovel insightsIntracellular poresGating mechanismFlexible linkerPore regionTRPV5
2016
Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase
Truong TH, Ung PM, Palde PB, Paulsen CE, Schlessinger A, Carroll KS. Molecular Basis for Redox Activation of Epidermal Growth Factor Receptor Kinase. Cell Chemical Biology 2016, 23: 837-848. PMID: 27427230, PMCID: PMC4958504, DOI: 10.1016/j.chembiol.2016.05.017.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorEpidermal growth factor receptor kinaseGrowth factor receptor kinaseDetailed functional analysisNew electrostatic interactionsFirst detailed functional analysisKinase regulationS-sulfenylationRedox biologyReceptor kinaseCatalytic loopGrowth factor receptorMolecular basisChronic oxidative stressKinase activityFunctional analysisCatalytic importanceRedox activationFactor receptorMajor classesOxidative stressCatalytic efficiencyData highlightMolecular dynamics simulationsActivation
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
2013
Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery
Paulsen CE, Carroll KS. Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery. Chemical Reviews 2013, 113: 4633-4679. PMID: 23514336, PMCID: PMC4303468, DOI: 10.1021/cr300163e.Peer-Reviewed Original Research
2011
Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity
Paulsen CE, Truong TH, Garcia FJ, Homann A, Gupta V, Leonard SE, Carroll KS. Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity. Nature Chemical Biology 2011, 8: 57-64. PMID: 22158416, PMCID: PMC3528018, DOI: 10.1038/nchembio.736.Peer-Reviewed Original Research
2009
Orchestrating Redox Signaling Networks through Regulatory Cysteine Switches
Paulsen CE, Carroll KS. Orchestrating Redox Signaling Networks through Regulatory Cysteine Switches. ACS Chemical Biology 2009, 5: 47-62. PMID: 19957967, PMCID: PMC4537063, DOI: 10.1021/cb900258z.Peer-Reviewed Original ResearchConceptsProtein functionReactive oxygen speciesIntracellular signal transductionCysteine switchRedox regulationSignal transductionCysteine oxidationCysteine residuesCurrent mechanistic insightsSecond messengerDiverse mechanismsMechanistic understandingMechanistic insightsOxygen speciesChemoselective oxidationNew therapeutic strategiesHydrogen peroxideRecent advancesOxidationTherapeutic strategiesTransductionSpeciesProteinMessengerResidues