2024
Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling
Mühlenbeck H, Tsutsui Y, Lemmon M, Bender K, Zipfel C. Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling. ELife 2024, 12: rp92110. PMID: 39028038, PMCID: PMC11259431, DOI: 10.7554/elife.92110.Peer-Reviewed Original ResearchConceptsKinase domainReceptor kinasePhosphorylation-dependent conformational changesActive conformationIntragenic suppressor mutationsCo-receptor BAK1Kinase-dead variantPlant receptor kinasesProtein kinase domainLeucine-rich repeatNon-catalytic functionsIntracellular kinase domainCo-receptorLRR-RKsSuppressor mutationsTrans-phosphorylationPseudokinase domainActivation loopActive kinaseAllosteric activationTransmembrane signalingBAK1Immune signalingRegulate signalingSignaling activityAllosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling
Mühlenbeck H, Tsutsui Y, Lemmon M, Bender K, Zipfel C. Allosteric activation of the co-receptor BAK1 by the EFR receptor kinase initiates immune signaling. ELife 2024, 12 DOI: 10.7554/elife.92110.4.Peer-Reviewed Original ResearchKinase domainReceptor kinasePhosphorylation-dependent conformational changesActive conformationIntragenic suppressor mutationsCo-receptor BAK1Kinase-dead variantPlant receptor kinasesProtein kinase domainLeucine-rich repeatNon-catalytic functionsIntracellular kinase domainCo-receptorLRR-RKsSuppressor mutationsTrans-phosphorylationPseudokinase domainActivation loopActive kinaseAllosteric activationTransmembrane signalingBAK1Immune signalingRegulate signalingSignaling activityDual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis
Shu S, Tsutsui Y, Nathawat R, Mi W. Dual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321510121. PMID: 38635633, PMCID: PMC11046580, DOI: 10.1073/pnas.2321510121.Peer-Reviewed Original ResearchConceptsLPS synthesisTetratricopeptide repeatCytoplasmic domainLevels of lipopolysaccharideCryo-EM structureGram-negative bacteriaLipopolysaccharide synthesisProtease FtsHRubredoxin domainLpxC activityTransmembrane helicesIn vivo analysisLpxCPseudomonas aeruginosaEnzymatic activityLapBFtsHAllosteric effectsYciMDual functionIn vitroTetratricopeptideAdaptorMotifDeacetylase
2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original Research
2021
Structural basis for ligand reception by anaplastic lymphoma kinase
Li T, Stayrook SE, Tsutsui Y, Zhang J, Wang Y, Li H, Proffitt A, Krimmer SG, Ahmed M, Belliveau O, Walker IX, Mudumbi KC, Suzuki Y, Lax I, Alvarado D, Lemmon MA, Schlessinger J, Klein DE. Structural basis for ligand reception by anaplastic lymphoma kinase. Nature 2021, 600: 148-152. PMID: 34819665, PMCID: PMC8639777, DOI: 10.1038/s41586-021-04141-7.Peer-Reviewed Original ResearchStructural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases
Sheetz J, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttila R, Preuss F, Suresh K, Stayrook S, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon M. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.02446.Peer-Reviewed Original ResearchReceptor tyrosine kinasesPseudokinase domainTyrosine kinaseTyrosine kinase-mediated signalingKey cellular processesKinase-mediated signalingExtracellular cuesViable drug targetTransduce signalsCellular processesEmbryonic developmentPseudokinasesTissue homeostasisFuture dissectionReceptor dimerizationStructural insightsKinase activityCancer hallmarksSignaling mechanismDrug targetsPutative routesKinaseOncogenic driversSmall moleculesPhosphotransfer
2017
Imatinib Binding to Human c-Src is Coupled to Inter-Domain Allostery and Suggest a Novel Kinase Inhibition Strategy
Tsutsui Y, Deredge D, Wintrode P, Hays F. Imatinib Binding to Human c-Src is Coupled to Inter-Domain Allostery and Suggest a Novel Kinase Inhibition Strategy. Biophysical Journal 2017, 112: 63a. DOI: 10.1016/j.bpj.2016.11.381.Peer-Reviewed Original Research
2016
Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy
Tsutsui Y, Deredge D, Wintrode P, Hays F. Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy. Scientific Reports 2016, 6: 30832. PMID: 27480221, PMCID: PMC4969603, DOI: 10.1038/srep30832.Peer-Reviewed Original ResearchConceptsHuman c-SrcC-SrcNon-receptor tyrosine kinase inhibitorsFunctional regulatory sitesC-Src SH3SH2 domainKinase domainHydrogen-deuterium exchangeKinase activationConformational dynamicsRegulatory sitesAllosteric siteMutation sitesKinase inhibitorsPatient tissuesInhibition strategiesAnti-neoplastic drugsPeptide ligandsDevelopment of TKICurrent study identifiesImatinib-resistant mutationsTyrosine kinase inhibitorsImatinib analogsMass spectrometryAllostery
2015
Conformation-Dependent Human p52Shc Phosphorylation by Human c‑Src
Tsutsui Y, Johnson J, Demeler B, Kinter M, Hays F. Conformation-Dependent Human p52Shc Phosphorylation by Human c‑Src. Biochemistry 2015, 54: 3469-3482. PMID: 25961473, DOI: 10.1021/acs.biochem.5b00122.Peer-Reviewed Original ResearchMeSH KeywordsCell MembraneCSK Tyrosine-Protein KinaseExtracellular Signal-Regulated MAP KinasesGRB2 Adaptor ProteinHumansMAP Kinase Signaling SystemPhosphatidylinositol PhosphatesPhosphorylationProtein StabilityProto-Oncogene Proteins p21(ras)Shc Signaling Adaptor ProteinsSrc Homology 2 Domain-Containing, Transforming Protein 1Src-Family KinasesConceptsHuman c-SrcMembrane-mimetic environmentsC-SrcPhosphorylation sitesAdaptor proteinGrb2 adaptor proteinPhosphorylation-dependent interactionPhosphorylation levelsRas/MAPKAmount of phosphorylationActive c-SrcCascade activationProtein phosphorylationMass spectrometry analysisComplex assemblyPhosphorylation statePhosphorylation statusP52ShcTyrosine residuesPhosphatidylinositol 4Tyrosine kinaseBiophysical characterizationInitial binding interactionGrb2Functional linkage
2014
Overproduction and biophysical characterization of human HSP70 proteins
Boswell-Casteel R, Johnson J, Duggan K, Tsutsui Y, Hays F. Overproduction and biophysical characterization of human HSP70 proteins. Protein Expression And Purification 2014, 106: 57-65. PMID: 25266791, PMCID: PMC4248018, DOI: 10.1016/j.pep.2014.09.013.Peer-Reviewed Original ResearchConceptsHuman HSP70 proteinHeat shock proteinsResponse pathwaysHSP70 proteinBiophysical characterizationFacilitate protein foldingVital cellular functionsInitial biophysical characterizationProtein-protein interactionsFuture biochemical studiesHeterologous overexpressionHSP functionCellular functionsProtein functionProtein foldingHSP70 familyFunctional characterizationConformational rearrangementsShock proteinsChemical stressorsHuman Hsp70HSP proteinsDownstream investigationsBiochemical studiesEscherichia coliHuman p52Shc Conformational Bias and Localization in c-SRC Activation
Tsutsui Y, Hays F. Human p52Shc Conformational Bias and Localization in c-SRC Activation. Biophysical Journal 2014, 106: 466a-467a. DOI: 10.1016/j.bpj.2013.11.2642.Peer-Reviewed Original Research
2012
Folding mechanism of the metastable serpin α1-antitrypsin
Tsutsui Y, Dela Cruz R, Wintrode P. Folding mechanism of the metastable serpin α1-antitrypsin. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 4467-4472. PMID: 22392975, PMCID: PMC3311335, DOI: 10.1073/pnas.1109125109.Peer-Reviewed Original Research
2011
Chapter Fifteen Probing Serpin Conformational Change Using Mass Spectrometry and Related Methods
Tsutsui Y, Sarkar A, Wintrode P. Chapter Fifteen Probing Serpin Conformational Change Using Mass Spectrometry and Related Methods. Methods In Enzymology 2011, 501: 325-350. PMID: 22078541, PMCID: PMC3679668, DOI: 10.1016/b978-0-12-385950-1.00015-8.Peer-Reviewed Original ResearchConceptsStructural mass spectrometry techniquesHydrogen/deuterium exchangeMass spectrometry techniquesDeuterium exchangeIon mobility mass spectrometrySpectrometry techniquesMass spectrometryMobility mass spectrometrySerpin polymersConformational flexibilitySerpin functionSerpin polymerizationChemical footprintingConformational changesThermodynamic metastabilitySpectrometryChapter FifteenSerpinsStructural distributionPolymerizationPolymersStabilityMisfoldingInhibitory mechanismFootprinting
2009
Local and Global Effects of a Cavity Filling Mutation in a Metastable Serpin
Sengupta T, Tsutsui Y, Wintrode P. Local and Global Effects of a Cavity Filling Mutation in a Metastable Serpin. Biochemistry 2009, 48: 8233-8240. PMID: 19624115, PMCID: PMC2746415, DOI: 10.1021/bi900342d.Peer-Reviewed Original Research
2008
The Structural Basis of Serpin Polymerization Studied by Hydrogen/Deuterium Exchange and Mass Spectrometry*
Tsutsui Y, Kuri B, Sengupta T, Wintrode P. The Structural Basis of Serpin Polymerization Studied by Hydrogen/Deuterium Exchange and Mass Spectrometry*. Journal Of Biological Chemistry 2008, 283: 30804-30811. PMID: 18794298, PMCID: PMC2576545, DOI: 10.1074/jbc.m804048200.Peer-Reviewed Original Research
2007
Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes
Tsutsui Y, Wintrode P. Cooperative Unfolding of a Metastable Serpin to a Molten Globule Suggests a Link Between Functional and Folding Energy Landscapes. Journal Of Molecular Biology 2007, 371: 245-255. PMID: 17568610, DOI: 10.1016/j.jmb.2007.05.039.Peer-Reviewed Original ResearchConceptsMutagenesis studiesEquilibrium unfoldingMolten globuleCooperative structural unitDramatic conformational changeMultiple structural domainsNumerous mutagenesis studiesExchange mass spectrometryStable native stateNon-cooperative transitionPrevious mutagenesis studiesMolten globule formHydrogen-deuterium exchangeEquilibrium molten globuleFunctional intermediatesProtease-serpin complexesStructural domainsTarget proteasesConformational changesMetastable SerpinNative stateEquilibrium intermediatesCooperative unfoldingUnfolded stateGlobule formHydrogen/deuterium exchange-mass spectrometry: a powerful tool for probing protein structure, dynamics and interactions.
Tsutsui Y, Wintrode P. Hydrogen/deuterium exchange-mass spectrometry: a powerful tool for probing protein structure, dynamics and interactions. Current Medicinal Chemistry 2007, 14: 2344-58. PMID: 17896983, DOI: 10.2174/092986707781745596.Peer-Reviewed Original ResearchConceptsProtein assembliesMolecular basisProtein structureNuclear magnetic resonance spectroscopyHydrogen/deuterium exchangeLarge protein assembliesD exchange processX-ray crystallographyDrugs/inhibitorsDynamics of proteinsBackbone amide hydrogensExchange processMagnetic resonance spectroscopyLocal structural environmentPatho-physiological processesViral capsid structureAmide hydrogensHXMSDeuterium exchangeMass spectrometrySmall sample requirementDrug designHigh-quality crystalsResonance spectroscopyProtein conformation
2006
The Conformational Dynamics of a Metastable Serpin Studied by Hydrogen Exchange and Mass Spectrometry
Tsutsui Y, Liu L, Gershenson A, Wintrode P. The Conformational Dynamics of a Metastable Serpin Studied by Hydrogen Exchange and Mass Spectrometry. Biochemistry 2006, 45: 6561-6569. PMID: 16716066, DOI: 10.1021/bi060431f.Peer-Reviewed Original Research