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 ResearchGlioblastoma 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 Research
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
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 fragmentsOrganelles
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 activatorReceptorsSequestrationProteinActivatorLigandsSpitzTGFTherapeuticsDomain
2007
Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators
Yaklichkin S, Vekker A, Stayrook S, Lewis M, Kessler D. Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators. BMC Genomics 2007, 8: 201. PMID: 17598915, PMCID: PMC1939712, DOI: 10.1186/1471-2164-8-201.Peer-Reviewed Original ResearchConceptsEh1-like motifsFox gene familyFox family proteinsFox proteinsGroucho interaction motifEh1 motifGene familyTranscriptional regulationFOX familyFamily proteinsInteraction motifsStructure predictionWinged helix DNA-binding domainFamily of transcriptional regulatorsSecondary structure predictionDNA-binding domainN-terminal motifSwiss protein databaseManual sequence alignmentFOX family genesDivergent speciesSequence alignmentProtein sequencesProtein databaseTranscriptional corepressor
2001
Crystal Structure of Human Type III 3α-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein Complexed with NADP+ and Ursodeoxycholate † , ‡
Jin Y, Stayrook S, Albert R, Palackal N, Penning T, Lewis M. Crystal Structure of Human Type III 3α-Hydroxysteroid Dehydrogenase/Bile Acid Binding Protein Complexed with NADP+ and Ursodeoxycholate † , ‡. Biochemistry 2001, 40: 10161-10168. PMID: 11513593, DOI: 10.1021/bi010919a.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAllosteric SiteAmino Acid SequenceBinding SitesCloning, MolecularComputer SimulationCrystallography, X-RayEscherichia coliFluoxetineHumansHydroxysteroid DehydrogenasesModels, MolecularMolecular ConformationMolecular Sequence DataNADPProtein BindingProtein Structure, SecondaryRecombinant ProteinsSequence AlignmentSequence Homology, Amino AcidUrsodeoxycholic AcidConceptsRat 3alpha-HSDAldo-keto reductase superfamilyBinding protein complexSteroid binding pocketAlpha/beta barrelBound NADP(+Human typeProtein complexesThree-dimensional structureOxyanion holeAndrogen 5alpha-dihydrotestosteroneBinding proteinStructural basisTransport of bile acidsAKR1C2Ternary complexRat isoformsNADP(+SuperfamilyExtended conformationProstatic productionActive siteIsoformsCrystal structureBile acids
1998
Steroidogenic Acute Regulatory Protein (StAR) Is A Sterol Transfer Protein*
Kallen C, Billheimer J, Summers S, Stayrook S, Lewis M, Strauss J. Steroidogenic Acute Regulatory Protein (StAR) Is A Sterol Transfer Protein*. Journal Of Biological Chemistry 1998, 273: 26285-26288. PMID: 9756854, DOI: 10.1074/jbc.273.41.26285.Peer-Reviewed Original ResearchConceptsSterol carrier protein-2Steroidogenic acute regulatory proteinStAR proteinRegulatory proteinsSterol transferCholesterol side-chain cleavage enzyme systemMitochondrial targeting sequenceSterol transfer activityTransfer proteinSterol transfer proteinsOuter mitochondrial membraneTrypsin-treated mitochondriaAmino acid residuesLipid transfer proteinsTransfer of cholesterolDonor membranesSubstrate cholesterolInner membraneMitochondrial membraneIsolated mitochondriaTarget sequenceN-terminalTemperature-dependent mannerAcid residuesPhosphatidylcholine transferSteroidogenic acute regulatory protein (StAR) acts on the outside of mitochondria to stimulate steroidogenesis
Arakane F, Kallen C, Watari H, Stayrook S, Lewis M, Strauss J. Steroidogenic acute regulatory protein (StAR) acts on the outside of mitochondria to stimulate steroidogenesis. Endocrine Research 1998, 24: 463-468. PMID: 9888526, DOI: 10.3109/07435809809032634.Peer-Reviewed Original ResearchConceptsCOS-1 cellsMitochondrial targeting sequenceWild-type StARSteroidogenic acute regulatory proteinHis-tagMitochondrial membraneIsolated mitochondriaN-terminal mitochondrial targeting sequenceTarget sequenceCOS-1Regulatory proteinsCytoplasm of transfected COS-1 cellsCholesterol side-chain cleavage systemLipoid congenital adrenal hyperplasiaSide-chain cleavage systemLocalized to mitochondriaInner mitochondrial membraneHis-tagged proteinsDelivery of cholesterolMitochondrial importPoint mutantsN-terminalStAR proteinCleavage systemE. coli