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 contextSenescenceImaging nanoscale-spatial oligomeric organization of membrane proteins directly from native membranes at single-molecule resolution
Walker G, Brown C, Ge X, Kumar S, Muzumdar M, Gupta K, Bhattacharyya M. Imaging nanoscale-spatial oligomeric organization of membrane proteins directly from native membranes at single-molecule resolution. Biophysical Journal 2024, 123: 348a. DOI: 10.1016/j.bpj.2023.11.2115.Peer-Reviewed Original ResearchDetermining the membrane recruitment mechanisms of peripheral membrane proteins through native mass spectrometry directly from tunable lipid membranes
McAllister R, Jung W, Bhattacharyya M, Gupta K. Determining the membrane recruitment mechanisms of peripheral membrane proteins through native mass spectrometry directly from tunable lipid membranes. Biophysical Journal 2024, 123: 90a. DOI: 10.1016/j.bpj.2023.11.665.Peer-Reviewed Original ResearchCapturing membrane snapshots: A quantitative proteome-wide guide for high-throughput spatially resolved extraction of membrane proteins for structural/functional studies on native membranes
Brown C, Ghosh S, McAllister R, Coleman J, Sun E, Zheng H, Kumar S, Panda A, Rothman J, Bhattacharyya M, Gupta K. Capturing membrane snapshots: A quantitative proteome-wide guide for high-throughput spatially resolved extraction of membrane proteins for structural/functional studies on native membranes. Biophysical Journal 2024, 123: 68a-69a. DOI: 10.1016/j.bpj.2023.11.487.Peer-Reviewed Original Research
2023
Oligomeric organization of membrane proteins from native membranes at nanoscale spatial and single-molecule resolution
Walker G, Brown C, Ge X, Kumar S, Muzumdar M, Gupta K, Bhattacharyya M. Oligomeric organization of membrane proteins from native membranes at nanoscale spatial and single-molecule resolution. Nature Nanotechnology 2023, 19: 85-94. PMID: 38012273, PMCID: PMC10981947, DOI: 10.1038/s41565-023-01547-4.Peer-Reviewed Original ResearchMembrane proteinsNative membranesOligomeric organizationDiverse membrane proteinsMembrane protein biologyNative cell membranesTarget membrane proteinsNative membrane environmentSingle-molecule resolutionSingle-molecule platformReceptor tyrosine kinasesOligomeric distributionNative nanodiscsOligomerization statusProtein biologySmall GTPaseGrowth factor bindingMembrane environmentOligomeric assembliesTyrosine kinaseCritical regulatorOncogenic mutationsCell membraneProteinMembraneOligomeric distribution of membrane proteins in native-membrane environment at nanoscale spatial and single-molecule resolution
Walker G, Brown C, Ge X, Gupta K, Muzumdar M, Bhattacharyya M. Oligomeric distribution of membrane proteins in native-membrane environment at nanoscale spatial and single-molecule resolution. Biophysical Journal 2023, 122: 457a. DOI: 10.1016/j.bpj.2022.11.2457.Peer-Reviewed Original Research
2022
Deciphering the molecular organization of Get pathway chaperones through native top-down dissociation of multi-protein complexes
Giska F, Mariappan M, Bhattacharyya M, Gupta K. Deciphering the molecular organization of Get pathway chaperones through native top-down dissociation of multi-protein complexes. Biophysical Journal 2022, 121: 333a. DOI: 10.1016/j.bpj.2021.11.1119.Peer-Reviewed Original Research
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 formActivationProtein Structure and Function: Looking through the Network of Side-Chain Interactions.
Bhattacharyya M, Ghosh S, Vishveshwara S. Protein Structure and Function: Looking through the Network of Side-Chain Interactions. Current Protein And Peptide Science 2016, 17: 4-25. PMID: 26412788, DOI: 10.2174/1389203716666150923105727.Peer-Reviewed Original ResearchConceptsNetwork theoryImportant problemComplex biological problemsProtein structure networksBipartite networksStructure networkEquilibrium structureModel validationDifferent schemesBiological problemsProblemNetwork approachTheoryNetwork metricsGeneral applicationComplex phenomenonGeneral featuresFormalismNetworkLarge numberProtein structureGeometrySpecific featuresBiological dataEnsemble
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
2013
An automated approach to network features of protein structure ensembles
Bhattacharyya M, Bhat CR, Vishveshwara S. An automated approach to network features of protein structure ensembles. Protein Science 2013, 22: 1399-1416. PMID: 23934896, PMCID: PMC3795498, DOI: 10.1002/pro.2333.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsComputational BiologyCrystallography, X-RayMethanocaldococcusModels, MolecularMolecular Dynamics SimulationNuclear Magnetic Resonance, BiomolecularProtein ConformationProteinsReceptors, Adrenergic, beta-2RNA, TransferSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSoftwareTyrosine-tRNA LigaseConceptsStructural ensemblesX-ray structureSide-chain interactionsNMR studiesSingle static structureChemical knowledgeMD trajectoriesLong-range allosteric communicationInteraction energyMultiple X-ray structuresDevelopment/applicationGeneral biological communityStructural dataStructure ensemblesProtein structureProgram packageStructureBiological relevanceProtein structure ensemblesAllosteric communicationAmino acidsTRNA complexHereinComplexesEasy accessRapid mass spectrometric determination of disulfide connectivity in peptides and proteins
Bhattacharyya M, Gupta K, Gowd KH, Balaram P. Rapid mass spectrometric determination of disulfide connectivity in peptides and proteins. Molecular Omics 2013, 9: 1340-1350. PMID: 23467691, DOI: 10.1039/c3mb25534d.Peer-Reviewed Original ResearchConceptsMass spectrometric fragmentationDisulfide connectivityRapid mass spectrometric determinationPeptide toxinsNatural peptide toxinsMass spectrometric determinationCID fragmentationSpectrometric determinationNatural peptidesProteolytic nickProteolytic peptidesDirect fragmentationUnambiguous characterisationDisulfide linkagesSubsequent determinationSynthetic analoguesRapid screeningMS profilesDisulfide crosslinksStraightforward approachNative disulfidesDeterminationPeptidesFoldamersIntact polypeptide
2012
Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach
Bhattacharyya M, Upadhyay R, Vishveshwara S. Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach. PLOS ONE 2012, 7: e51676. PMID: 23284738, PMCID: PMC3524241, DOI: 10.1371/journal.pone.0051676.Peer-Reviewed Original Research
2011
Probing the Allosteric Mechanism in Pyrrolysyl-tRNA Synthetase Using Energy-Weighted Network Formalism
Bhattacharyya M, Vishveshwara S. Probing the Allosteric Mechanism in Pyrrolysyl-tRNA Synthetase Using Energy-Weighted Network Formalism. Biochemistry 2011, 50: 6225-6236. PMID: 21650159, DOI: 10.1021/bi200306u.Peer-Reviewed Original ResearchConceptsPyrrolysyl-tRNA synthetaseDimeric proteinFunctioning of proteinsSequence/structureAllosteric regulationAllosteric communicationAnticodon recognitionTRNA synthetasesImportant residuesAllosteric mechanismKey residuesSubtle rearrangementsProteinKey playersPyrrolysineFunctional aspectsSynthetaseResiduesAtypical enzymeGlobal perturbationsComprehensive viewComplexesStructure networkMolecular dynamics simulationsPylRSQuantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of protein – ligand interactions
Bhattacharyya M, Vishveshwara S. Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of protein – ligand interactions. Molecular Omics 2011, 7: 2320-2330. PMID: 21617814, DOI: 10.1039/c1mb05038a.Peer-Reviewed Original ResearchConceptsConformational ensemblesPyrrolysyl-tRNA synthetaseProtein conformational ensemblesImportant biological phenomenaRNA/DNA complexesProtein-ligand interactionsProtein foldingLigand induced variationsConformational populationsDifferent ligandsMD simulation trajectoriesDNA complexesAmino acidsBiological phenomenaSuch subtle changesD. hafnienseSimulation trajectoriesEnzyme catalysisBackbone levelProteinAtomistic detailsNetwork analysisMD snapshotsMolecular dynamics simulationsObjective clustering
2010
Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis
Bhattacharyya M, Vishveshwara S. Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis. BMC Molecular And Cell Biology 2010, 10: 27. PMID: 20704697, PMCID: PMC2929236, DOI: 10.1186/1472-6807-10-27.Peer-Reviewed Original ResearchConceptsFree energy landscapeConformational changesActive siteDifferent conformationsConformational free energy landscapeAutoinducer-2 productionStructure network analysisDynamics of waterBacterial quorum sensingMolecular dynamics simulationsDetailed molecular levelFree energy changeEnergy landscapeFree energy evaluationEnzyme catalysisQuorum sensingDimeric proteinSimulation trajectoriesDifferent ligandsDynamics simulationsMechanistic featuresLigandsMolecular levelInactive formMechanistic details