2024
A painful paradox: How a drastic TRPA1 truncation confers gain-of-function
Bali A, Schaefer S, Trier I, Zhang A, Kabeche L, Paulsen C. A painful paradox: How a drastic TRPA1 truncation confers gain-of-function. Biophysical Journal 2024, 123: 37a. DOI: 10.1016/j.bpj.2023.11.314.Peer-Reviewed Original Research
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
2018
155 Loss of PRDX1 increases RAD51 Cys319 oxidation and decreases homologous recombination
Skoko J, Asan A, Woodcock C, Cao J, Gaboriau D, Paulsen C, Attar M, Wingert B, Woodcock S, Schulte J, Ma H, Camacho C, Liu Y, Morrison C, Carroll K, Freeman B, Neumann C. 155 Loss of PRDX1 increases RAD51 Cys319 oxidation and decreases homologous recombination. Free Radical Biology And Medicine 2018, 128: s73-s74. DOI: 10.1016/j.freeradbiomed.2018.10.159.Peer-Reviewed Original ResearchRAD51 foci formationDNA double-strand breaksHomologous recombinationPeroxiredoxin 1Foci formationSuppression of HRDNA damageSulfenic acid formDouble-strand breaksSite-directed mutagenesisSoft agar colony formationAgar colony formationMDA-MB-231 breast cancer cellsGenomic stabilityBind RAD51DNA repairImmunoprecipitation assaysCell signalingOxidation of cysteineRAD51Bind proteinsC319Enhanced DNA damageBreast cancer cellsProtein sensors
2017
138 Redox Regulation of RAD51 and Homologous Recombination by Peroxiredoxin 1 and Electrophilic Nitro-fatty Acids
Skoko J, Asan A, Woodcock C, Cao J, Gaboriau D, Paulsen C, Attar M, Wingert B, Woodcock S, Schulte J, Ma H, Camacho C, Liu Y, Morrison C, Carroll K, Freeman B, Neumann C. 138 Redox Regulation of RAD51 and Homologous Recombination by Peroxiredoxin 1 and Electrophilic Nitro-fatty Acids. Free Radical Biology And Medicine 2017, 112: 100-101. DOI: 10.1016/j.freeradbiomed.2017.10.151.Peer-Reviewed Original ResearchOA-NO2Breast cancer cellsPeroxiredoxin 1Sensitization of cellsElectrophilic nitro-fatty acidsCancer cellsHuman breast cancer cellsNitro-fatty acidsPharmacological treatmentBreast cancerDNA damageRAD51 foci formationFoci formationCancerDNA double-strand breaksHomologous recombination repairPrimary targetSensitizationRepairCellsCellular responsesH2AX phosphorylationRecombination repairHomologous recombinationRedox regulationA 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 simulationsActivationStructure of the TRPA1 Ion Channel Suggests Regulatory Mechanisms
Paulsen C, Armache J, Gao Y, Cheng Y, Julius D. Structure of the TRPA1 Ion Channel Suggests Regulatory Mechanisms. Biophysical Journal 2016, 110: 26a. DOI: 10.1016/j.bpj.2015.11.202.Peer-Reviewed Original Research
2015
Erratum: Structure of the TRPA1 ion channel suggests regulatory mechanisms
Paulsen C, Armache J, Gao Y, Cheng Y, Julius D. Erratum: Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 2015, 525: 552-552. PMID: 26200340, DOI: 10.1038/nature14871.Peer-Reviewed Original ResearchStructure 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 strategiesTransductionSpeciesProteinMessengerResiduesChemical Dissection of an Essential Redox Switch in Yeast
Paulsen CE, Carroll KS. Chemical Dissection of an Essential Redox Switch in Yeast. Cell Chemical Biology 2009, 16: 217-225. PMID: 19230722, DOI: 10.1016/j.chembiol.2009.01.003.Peer-Reviewed Original ResearchConceptsSulfenic acidCell-permeable chemical probesSulfenic acid modificationCysteine sulfenic acid modificationTranscription factor Yap1Chemical probesCysteine oxidationRedox switchElectrostatic calculationsIntermolecular disulfide formationCharge distributionHydrogen peroxideAcid modificationNuclear accumulationIntermolecular disulfideConformational rearrangementsDisulfide formationCentral unresolved questionYAP1 activationYAP1GPX3Chemical dissectionCatalysisUnresolved questionsAcid