Steve Stayrook
Associate Research Scientist in PharmacologyCards
About
Research
Publications
2025
Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling
Li T, Stayrook S, Li W, Wang Y, Li H, Zhang J, Liu Y, Klein D. Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling. Nature Communications 2025, 16: 3580. PMID: 40234450, PMCID: PMC12000326, DOI: 10.1038/s41467-025-58828-w.Peer-Reviewed Original ResearchConceptsThrombospondin type I repeatsIsthmin-1Pre-adipocytesType I repeatsBacterial streptavidinSurface helicesI repeatsMolecular detailsDiverse functionsFunctional studiesAkt phosphorylationFunctional roleStructural plasticityInsulin-like propertiesCrystal structureAMOPGrowth factorDomainPhosphorylationApoptosisLiver steatosisProteinHelixAktStreptavidinStructural 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 ResearchConceptsFibronectin type IIIExtracellular regionReceptor tyrosine kinasesR7 photoreceptor cellsN-terminal domainCryo-EM structureC-terminal peptideDownstream Signaling PathwaysDrosophila homologueBeta-strandsHelical hairpinHuman orthologHydrogen-deuterium exchange mass spectrometryMutagenesis studiesStructural basisRegulatory functionsSignaling pathwayTyrosine kinaseLigand bindingSevenlessComplex predictionBinding epitopeHDX-MSPhotoreceptor cellsBinding interactions
2024
Structural insights into the role and targeting of EGFRvIII
Bagchi A, Stayrook S, Xenaki K, Starbird C, Doulkeridou S, El Khoulati R, Roovers R, Schmitz K, van Bergen En Henegouwen P, Ferguson K. Structural insights into the role and targeting of EGFRvIII. Structure 2024, 32: 1367-1380.e6. PMID: 38908376, PMCID: PMC11380598, DOI: 10.1016/j.str.2024.05.018.Peer-Reviewed Original Research
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 ResearchRational design of photosynthetic reaction center protein maquettes
Ennist N, Stayrook S, Dutton P, Moser C. Rational design of photosynthetic reaction center protein maquettes. Frontiers In Molecular Biosciences 2022, 9: 997295. PMID: 36213121, PMCID: PMC9532970, DOI: 10.3389/fmolb.2022.997295.Peer-Reviewed Original ResearchNatural photosystemsCrystal structureSolar-to-fuel energy conversionAssemble metal ionsElectron-transfer reactionsPhotosynthetic charge separationPhotosynthetic reaction centersCharge separationElectron tunneling theoryChemical fuelsMetal ionsReaction centerElectron donorHolo-stateStructural transitionEnergy conversionElectron acceptorModular strategySpectroscopic assaysReactionPhoton energyCrystalState of assemblyProtein designProduction of biofuelsDe novo protein design of photochemical reaction centers
Ennist N, Zhao Z, Stayrook S, Discher B, Dutton P, Moser C. De novo protein design of photochemical reaction centers. Nature Communications 2022, 13: 4937. PMID: 35999239, PMCID: PMC9399245, DOI: 10.1038/s41467-022-32710-5.Peer-Reviewed Original ResearchConceptsCharge separationSolar-to-fuel energy conversionReaction centerLight-driven charge separationX-ray crystal structurePhotosynthetic reaction center proteinCharge separation lifetimeSolar fuel productionTransient absorption spectroscopyPhotosynthetic reaction centersPhotochemical charge separationModify natural proteinsPhotochemical reaction centerReaction center proteinCluster oxidationRedox centersCrystal structureAbsorption spectroscopyElectron transfer activityNatural protein structuresDe novo protein designPhotosynthetic protein complexesEnergy conversionX-rayProtein frameworkGlioblastoma mutations alter EGFR dimer structure to prevent ligand bias
Hu C, Leche CA, Kiyatkin A, Yu Z, Stayrook SE, Ferguson KM, Lemmon MA. Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias. Nature 2022, 602: 518-522. PMID: 35140400, PMCID: PMC8857055, DOI: 10.1038/s41586-021-04393-3.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 ResearchROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes
Shi F, Mendrola JM, Sheetz JB, Wu N, Sommer A, Speer KF, Noordermeer JN, Kan ZY, Perry K, Englander SW, Stayrook SE, Fradkin LG, Lemmon MA. ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes. Cell Reports 2021, 37: 109834. PMID: 34686333, PMCID: PMC8650758, DOI: 10.1016/j.celrep.2021.109834.Peer-Reviewed Original ResearchAnimalsDrosophila melanogasterDrosophila ProteinsModels, MolecularNerve Tissue ProteinsProtein BindingProtein ConformationProtein Interaction Domains and MotifsProtein-Tyrosine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSf9 CellsStructure-Activity RelationshipWnt ProteinsWnt Signaling PathwayStructural 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