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
2020
Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases
Sheetz JB, Mathea S, Karvonen H, Malhotra K, Chatterjee D, Niininen W, Perttilä R, Preuss F, Suresh K, Stayrook SE, Tsutsui Y, Radhakrishnan R, Ungureanu D, Knapp S, Lemmon MA. Structural Insights into Pseudokinase Domains of Receptor Tyrosine Kinases. Molecular Cell 2020, 79: 390-405.e7. PMID: 32619402, PMCID: PMC7543951, DOI: 10.1016/j.molcel.2020.06.018.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBaculoviridaeBinding SitesCell Adhesion MoleculesCell LineCloning, MolecularCrystallography, X-RayGene ExpressionHumansMiceModels, MolecularPrecursor Cells, B-LymphoidProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsProtein Kinase InhibitorsReceptor Protein-Tyrosine KinasesReceptor Tyrosine Kinase-like Orphan ReceptorsReceptors, Eph FamilyRecombinant ProteinsSf9 CellsSmall Molecule LibrariesSpodopteraStructural Homology, ProteinSubstrate SpecificityConceptsInsulin receptor kinasePseudokinase domainReceptor tyrosine kinasesTyrosine kinaseNon-catalytic functionsATP-binding pocketType II inhibitorsDomain plasticityActivation loopReceptor kinaseInactive conformationStructural insightsPseudokinasesATP siteStructural comparisonAromatic residuesKinaseAlternative interactionsApparent lackImportant roleDomainWntMotifROR1Residues
2018
Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass
Gunaratne R, Kumar S, Frederiksen J, Stayrook S, Lohrmann J, Perry K, Bompiani K, Chabata C, Thalji N, Ho M, Arepally G, Camire R, Krishnaswamy S, Sullenger B. Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass. Nature Biotechnology 2018, 36: 606-613. PMID: 29863725, PMCID: PMC6349032, DOI: 10.1038/nbt.4153.Peer-Reviewed Original Research
2016
Structural Basis for the Procofactor to Cofactor Transition in Human Factor V
Kumar S, Deng W, Stayrook S, Li R, Camire R, Krishnaswamy S. Structural Basis for the Procofactor to Cofactor Transition in Human Factor V. Blood 2016, 128: 253. DOI: 10.1182/blood.v128.22.253.253.Peer-Reviewed Original ResearchBasic regionB domainC-terminusLong standing puzzleBR bindingCrystal structureDocking studiesBr fragmentsHuman factor VCentral B domainA2 domainAmide proton exchange ratesPhosphatidylserine-containing membranesAr2Hydrogen-deuterium exchangeA1-A2-B-A3-C1-C2Adjacent regionsAmide proton exchangeComputational docking studiesProton exchange ratesDomain organizationAcid sequenceProteolytic excisionCofactor formationPrimary structure
2015
The X-Ray Structure of a Variant of Human Factor V Provides Structural Insights into the Procofactor Activation Paradox
Kumar S, Stayrook S, Camire R, Krishnaswamy S. The X-Ray Structure of a Variant of Human Factor V Provides Structural Insights into the Procofactor Activation Paradox. Blood 2015, 126: 121. DOI: 10.1182/blood.v126.23.121.121.Peer-Reviewed Original ResearchB domainAcid regionC-terminusCofactor functionBR bindingDiffraction quality crystalsCoagulation factor VA3 domainFactor VaCofactor activityHomologous A domainsA1-A2-B-A3-C1-C2Ca2+-dependent fashionDomain organizationMolecular replacementAcid sequenceXa bindingSingle chain antibodyPrimary sequenceProteolytic excisionDevelopment of novel strategiesBind calcium ionsProteolytic processingProteolytic cleavageStructure-based model
2014
New Structural Insights into High Affinity Membrane Binding By Coagulation Factor V/Va
Kumar S, Stayrook S, Huntington J, Camire R, Krishnaswamy S. New Structural Insights into High Affinity Membrane Binding By Coagulation Factor V/Va. Blood 2014, 124: 4216. DOI: 10.1182/blood.v124.21.4216.4216.Peer-Reviewed Original ResearchSmall-angle X-ray scattering envelopeMembrane bindingPS-containing membranesC-domainMembrane binding functionMembrane-bound configurationHigh-affinity membrane bindingX-ray structureC2 domainBinding to membranesFactor VaBinding variantsBinding to PS-containing membranesC1 domainV-formBinding functionSmall-angle X-ray scatteringConformational rearrangementsEnergetic expenditureMembrane affinityStructural insightsAffinity interactionSites of vascular damageConformational changesPublished structuresX-Ray Structure of an Anticoagulant RNA Aptamer Bound to Factor Xa. Structural Basis for Its Ability to Disrupt Interactions Between Xa and Va within Prothrombinase
Kumar S, Sullenger B, Stayrook S, Krishnaswamy S. X-Ray Structure of an Anticoagulant RNA Aptamer Bound to Factor Xa. Structural Basis for Its Ability to Disrupt Interactions Between Xa and Va within Prothrombinase. Blood 2014, 124: 4232. DOI: 10.1182/blood.v124.21.4232.4232.Peer-Reviewed Original ResearchRNA aptamersC-terminusBinding to factor VIIIaIntrinsic XaseBase-paired stemActive site functionAssembly of prothrombinaseFactor Xa and factor VaSELEX screeningMolecular replacementInteracting proteinsProteinase domainFunctional characterizationAptamer bindingCatalytic Ser195Disrupt interactionsA-resolutionFactor XaHeparin bindingStructural basisAutolysis loopNucleotideInteracting speciesNucleotide basesSolvent accessible surface area
2012
Crystal Structure of a Proteolytic Fragment of ADAMTS13 Reveals Alternative Disulfide Pairings in the Cysteine-Rich Domain
Skipwith C, Stayrook S, Rottensteiner H, Scheiflinger F, Zheng X. Crystal Structure of a Proteolytic Fragment of ADAMTS13 Reveals Alternative Disulfide Pairings in the Cysteine-Rich Domain. Blood 2012, 120: 3363. DOI: 10.1182/blood.v120.21.3363.3363.Peer-Reviewed Original ResearchIntermolecular disulfide bondsSpacer domainExosite interactionsProteolytic fragmentsDisulfide bondsNon-catalytic domainStably transfected Chinese hamster ovary cellsCysteine-rich domainChinese hamster ovary cellsDisulfide pairing patternADAMTS13 spacer domainHamster ovary cellsCys-richCrystallization screeningCysteine residuesDiffracting crystalsVon Willebrand factorX-ray diffractionFree cysteine residuesDisulfide bond pairingsDisulfide pairingPairing patternsCA domainOvary cellsResidues
2011
High Resolution X-Ray Structure of Snake Venom Factor V: Evolution of a Hemostatic Cofactor to a Toxin Poised to Inflict Maximal Damage to Mammalian Blood Coagulation
Kumar S, Stayrook S, Huntington J, Camire R, Krishnaswamy S. High Resolution X-Ray Structure of Snake Venom Factor V: Evolution of a Hemostatic Cofactor to a Toxin Poised to Inflict Maximal Damage to Mammalian Blood Coagulation. Blood 2011, 118: 375. DOI: 10.1182/blood.v118.21.375.375.Peer-Reviewed Original ResearchC2 domainA2 domainVenom proteinsB domainVenom of Pseudonaja textilisMembrane-dependent reactionsA1-A2-B-A3-C1-C2Absence of membranesMammalian coagulationSequence alignmentMammalian blood coagulationDomain organizationMolecular replacementRegulating blood coagulationToxin repertoireProtruding loopBinding to membranesHydrophobic residuesProteolytic processingBind membranesResolution structureMembrane bindingA-resolutionActivation of human prothrombinProteolytic activity
2009
N-terminal Domains Elicit Formation of Functional Pmel17 Amyloid Fibrils*
Watt B, van Niel G, Fowler DM, Hurbain I, Luk KC, Stayrook SE, Lemmon MA, Raposo G, Shorter J, Kelly JW, Marks MS. N-terminal Domains Elicit Formation of Functional Pmel17 Amyloid Fibrils*. Journal Of Biological Chemistry 2009, 284: 35543-35555. PMID: 19840945, PMCID: PMC2790984, DOI: 10.1074/jbc.m109.047449.Peer-Reviewed Original ResearchConceptsFibril formationFormation of melanosomesMultivesicular compartmentsImperfect repeatsRPT domainTransmembrane proteinMelanosome maturationTerminal domainIntracellular traffickingMultivesicular bodiesAmyloid foldPrecursor organellesAmyloid-like fibrilsDownstream domainSubcellular organellesAmyloid conversionRegulatory rolePmel17RepeatsEarly stepsStructural coreAmyloid formationProteolytic fragmentsRecombinant fragmentsOrganellesStructural basis for EGFR ligand sequestration by Argos
Klein D, Stayrook S, Shi F, Narayan K, Lemmon M. Structural basis for EGFR ligand sequestration by Argos. The FASEB Journal 2009, 23: 883.7-883.7. DOI: 10.1096/fasebj.23.1_supplement.883.7.Peer-Reviewed Original ResearchEpidermal growth factor receptorHuman urokinase-type plasminogen activator receptorDiverse developmental processesClamp-like structureEGF-like domainGrowth factor ligandsArgos functionMammalian counterpartsLigand sequestrationEGF-like modulesUrokinase-type plasminogen activator receptorEGF domainsEGF ligandGrowth factor receptorEssential regulatorStructural basisDevelopmental processesStructural homologuesEGFR ligandsFactor ligandHuman cancersPlasminogen activator receptorFactor receptorErbB/Inappropriate activation
2008
Structural basis for EGFR ligand sequestration by Argos
Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA. Structural basis for EGFR ligand sequestration by Argos. Nature 2008, 453: 1271-1275. PMID: 18500331, PMCID: PMC2526102, DOI: 10.1038/nature06978.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell LineCrystallography, X-RayDrosophila melanogasterDrosophila ProteinsEpidermal Growth FactorErbB ReceptorsEye ProteinsHumansLigandsMembrane ProteinsModels, MolecularNerve Tissue ProteinsProtein Structure, TertiaryReceptors, Transforming Growth Factor betaSpodopteraConceptsEpidermal growth factor receptorLigand sequestrationEGFR ligand SpitzLigand SpitzMammalian counterpartsGrowth factor receptorStructural basisUrokinase plasminogen activatorStructural homologuesEGFR ligandsFactor receptorAnticancer therapeuticsStructural resemblanceHomologuesPlasminogen activatorReceptorsSequestrationProteinActivatorLigandsSpitzTGFTherapeuticsDomainCrystal structure of the λ repressor and a model for pairwise cooperative operator binding
Stayrook S, Jaru-Ampornpan P, Ni J, Hochschild A, Lewis M. Crystal structure of the λ repressor and a model for pairwise cooperative operator binding. Nature 2008, 452: 1022-1025. PMID: 18432246, DOI: 10.1038/nature06831.Peer-Reviewed Original Research