2020
Flexible 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
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