2018
Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain
Emptage RP, Lemmon MA, Ferguson KM, Marmorstein R. Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain. Structure 2018, 26: 1137-1143.e3. PMID: 30099988, PMCID: PMC6092042, DOI: 10.1016/j.str.2018.05.008.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCheckpoint Kinase 1Cloning, MolecularCrystallography, X-RayEscherichia coliGene ExpressionGenetic VectorsHumansKineticsModels, MolecularMutationPeptidesProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsProtein Serine-Threonine KinasesRecombinant ProteinsStructural Homology, ProteinSubstrate SpecificityThermodynamicsConceptsKA1 domainSer/Thr protein kinaseKinase structureRelated kinasesUBA domainKinase domainProtein kinaseStructural basisC-terminusUnexpected interfaceC-lobeKinaseΑD helixPotential new avenuesAutoinhibitoryData implicateDomain surfaceDomainNew avenuesYeastAutoinhibitionCrystal structureHelixAlzheimer's diseaseVariants
2017
EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics
Freed DM, Bessman NJ, Kiyatkin A, Salazar-Cavazos E, Byrne PO, Moore JO, Valley CC, Ferguson KM, Leahy DJ, Lidke DS, Lemmon MA. EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics. Cell 2017, 171: 683-695.e18. PMID: 28988771, PMCID: PMC5650921, DOI: 10.1016/j.cell.2017.09.017.Peer-Reviewed Original ResearchMeSH KeywordsCrystallography, X-RayEpigenEpiregulinErbB ReceptorsFluorescence Resonance Energy TransferHumansKineticsLigandsModels, MolecularProtein MultimerizationConceptsReceptor tyrosine kinasesEpidermal growth factor receptorEGFR ligandsEGFR extracellular regionG protein-coupled receptorsDifferent EGFR ligandsCellular programsDifferent activating ligandsEGFR dimersCell signalingGrowth factor receptorExtracellular regionDimeric conformationEGFR dimerizationNew therapeutic opportunitiesReceptor dimersTyrosine kinaseBreast cancer cellsDimerization strengthActivating ligandsFactor receptorCancer cellsEpigenTherapeutic opportunitiesBiased agonismIntramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase–associated 1 domain
Emptage RP, Schoenberger MJ, Ferguson KM, Marmorstein R. Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase–associated 1 domain. Journal Of Biological Chemistry 2017, 292: 19024-19033. PMID: 28972186, PMCID: PMC5704483, DOI: 10.1074/jbc.m117.811265.Peer-Reviewed Original ResearchConceptsKA1 domainIntramolecular autoinhibitionSer/Thr proteinKinase 1N-terminal kinase domainChk1 kinase activityKey regulatory mechanismTerminal regulatory regionDNA damage repairSite-directed mutagenesisCheckpoint kinase 1Thr proteinChk1 kinaseHuman Chk1Truncation mutantsKinase domainRegulatory regionsKinase activityBasic residuesDamage repairRegulatory mechanismsStructural homologyResidue linkerCell cyclePrimary structure