2024
Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging
Occean J, Yang N, Sun Y, Dawkins M, Munk R, Belair C, Dar S, Anerillas C, Wang L, Shi C, Dunn C, Bernier M, Price N, Kim J, Cui C, Fan J, Bhattacharyya M, De S, Maragkakis M, de Cabo R, Sidoli S, Sen P. Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging. Nature Communications 2024, 15: 6357. PMID: 39069555, PMCID: PMC11284234, DOI: 10.1038/s41467-024-50725-y.Peer-Reviewed Original ResearchConceptsTissue-specific functionsDNA hydroxymethylationMagnitude of transcriptional changesAlternative splicing eventsMagnitude of gene expression changesTissue-specific genesGene expression changesGene bodiesSplicing eventsDNA methylationModel organismsTranscriptional changesExpression changesGenesAge-related diseasesFunctional roleMouse liverHuman tissuesProlonged quiescenceRestriction functionSplicingDNAMiceAge-related contextSenescence
2020
Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase
Karandur D, Bhattacharyya M, Xia Z, Lee YK, Muratcioglu S, McAffee D, McSpadden E, Qiu B, Groves JT, Williams ER, Kuriyan J. Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase. ELife 2020, 9: e57784. PMID: 32902386, PMCID: PMC7538161, DOI: 10.7554/elife.57784.Peer-Reviewed Original ResearchConceptsRegulatory segmentDependent protein kinase IIExchange of subunitsProtein kinase IIMammalian cellsFluorescence intensity analysisKinase IIOligomeric enzymesHoloenzymePhosphorylated peptidesNeuronal signalingSmall oligomersActive stateSubunitsCaMKIIActivationCrucial roleMolecular dynamics simulationsMass spectrometryKinasePhosphorylationSignalingHub structureBindsEnzymeFlexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation
Bhattacharyya M, Lee YK, Muratcioglu S, Qiu B, Nyayapati P, Schulman H, Groves JT, Kuriyan J. Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation. ELife 2020, 9: e53670. PMID: 32149607, PMCID: PMC7141811, DOI: 10.7554/elife.53670.Peer-Reviewed Original ResearchConceptsInhibitory autophosphorylationResidue linkerDependent protein kinase IISingle-molecule assaysMammalian cell expressionProtein kinase IICaMKII variantsShort linkerTransphosphorylation ratesKinase domainCaMKII holoenzymeKinase IIAutophosphorylationHoloenzymeFlexible linkerPrincipal isoformCalcium signalsRelative levelsIsoformsCaMKIIHuman CaCell expressionLinkerVariantsSequence
2019
Structural Insights into the Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII).
Bhattacharyya M, Karandur D, Kuriyan J. Structural Insights into the Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII). Cold Spring Harbor Perspectives In Biology 2019, 12: a035147. PMID: 31653643, PMCID: PMC7263085, DOI: 10.1101/cshperspect.a035147.Peer-Reviewed Original ResearchConceptsDependent protein kinase IIProtein kinase IIKinase domainKinase IISerine/threonine kinaseSpecialized isoformIntact holoenzymeThreonine kinaseCaMKII functionCaMKII holoenzymeSubunit exchangeStructural insightsRecent electron microscopic investigationsCaMKII activityStructural mechanismsFlexible linkerCardiac signalingCentral hubHoloenzymeCaMKIICurrent understandingKey roleKinaseSignalingElectron microscopic investigations
2017
Deconstruction of the Ras switching cycle through saturation mutagenesis
Bandaru P, Shah NH, Bhattacharyya M, Barton JP, Kondo Y, Cofsky JC, Gee CL, Chakraborty AK, Kortemme T, Ranganathan R, Kuriyan J. Deconstruction of the Ras switching cycle through saturation mutagenesis. ELife 2017, 6: e27810. PMID: 28686159, PMCID: PMC5538825, DOI: 10.7554/elife.27810.Peer-Reviewed Original ResearchConceptsInactive stateNucleotide exchange factorsDeep mutational scanningVertebrate lineageSequence conservationRas proteinsEvolutionary analysisHigh conservationExchange factorMutational toleranceRas dynamicsMutational effectsSelection pressureMutational scanningGlobal selection pressureSaturation mutagenesisMutational dataRas sequencesProteinBiochemical analysisBiochemical networksMechanistic explanationRegulatorMutationsConservation
2016
Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II
Bhattacharyya M, Stratton MM, Going CC, McSpadden ED, Huang Y, Susa AC, Elleman A, Cao YM, Pappireddi N, Burkhardt P, Gee CL, Barros T, Schulman H, Williams ER, Kuriyan J. Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II. ELife 2016, 5: e13405. PMID: 26949248, PMCID: PMC4859805, DOI: 10.7554/elife.13405.Peer-Reviewed Original ResearchConceptsDependent protein kinase IIProtein kinase IICaMKII holoenzymeKinase IIExchange of subunitsKinase domainSubunit exchangeIntersubunit interfaceMolecular mechanismsOligomeric enzymesHoloenzymeHub interfaceCalmodulinCaMKIIThree-way competitionUnactivated onesDimersDodecamericSubunitsOrganismsEnzymeHubMechanismSpiral formActivation
2014
Activation-triggered subunit exchange between CaMKII holoenzymes facilitates the spread of kinase activity
Stratton M, Lee IH, Bhattacharyya M, Christensen SM, Chao LH, Schulman H, Groves JT, Kuriyan J. Activation-triggered subunit exchange between CaMKII holoenzymes facilitates the spread of kinase activity. ELife 2014, 3: e01610. PMID: 24473075, PMCID: PMC3901001, DOI: 10.7554/elife.01610.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateBinding SitesCalcium-Calmodulin-Dependent Protein Kinase Type 2CalmodulinCatalytic DomainEnzyme ActivationEnzyme StabilityHoloenzymesHumansKineticsMicroscopy, FluorescenceMolecular Docking SimulationMolecular Dynamics SimulationPhosphorylationProtein BindingProtein Structure, QuaternaryProtein SubunitsRecombinant ProteinsSignal TransductionThreonineConceptsExchange of subunitsActivation of CaMKIICalcium-independent phosphorylationRegulatory segmentNew subunitsCaMKII holoenzymeThr-305Subunit exchangeKinase activityHoloenzymeNeuronal signalingCentral hubCaMKIIPhosphorylationSubunitsMemory formationActivationMolecular dynamics simulationsUnactivated onesDodecamericSignalingCalmodulinInteractsResiduesMicroscopy techniques
2009
Allostery and conformational free energy changes in human tryptophanyl‐tRNA synthetase from essential dynamics and structure networks
Bhattacharyya M, Ghosh A, Hansia P, Vishveshwara S. Allostery and conformational free energy changes in human tryptophanyl‐tRNA synthetase from essential dynamics and structure networks. Proteins Structure Function And Bioinformatics 2009, 78: 506-517. PMID: 19768679, DOI: 10.1002/prot.22573.Peer-Reviewed Original ResearchConceptsHuman tryptophanyl-tRNA synthetaseTryptophanyl-tRNA synthetaseConcept of allosteryProtein structure networksProtein complexesMultidomain proteinsAllosteric communicationFunctional insightsProtein biosynthesisCognate tRNAAllosteric mechanismAllosteryConformational free energy changesEnzymatic catalysisConformational mobilityFlexible regionsMolecular levelAmino acidsProteinStructure networkMolecular-level understandingFree energy landscapePopulation shiftsMolecular dynamics simulationsFree energy change