Yuko Tsutsui
Research Scientist in PharmacologyCards
About
Research
Publications
2025
Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS
Zhang J, Tsutsui Y, Li H, Li T, Wang Y, Laraki S, Alarcon-Frias S, Stayrook S, Klein D. Structural basis for the interaction between the Drosophila RTK Sevenless (dROS1) and the GPCR BOSS. Nature Communications 2025, 16: 808. PMID: 39827240, PMCID: PMC11743138, DOI: 10.1038/s41467-025-55943-6.Peer-Reviewed Original Research
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