Intramolecular 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 structureMolecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase.
Emptage RP, Lemmon MA, Ferguson KM. Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid activation of MARK1 kinase. Biochemical Journal 2017, 474: 385-398. PMID: 27879374, PMCID: PMC5317272, DOI: 10.1042/bcj20160792.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsBinding SitesCloning, MolecularEnzyme AssaysEscherichia coliGene ExpressionHumansKineticsMitogen-Activated Protein Kinase 1Models, MolecularPeptidesPhospholipidsProtein BindingProtein Interaction Domains and MotifsProtein Structure, SecondaryRecombinant ProteinsScattering, Small AngleSubstrate SpecificityX-Ray DiffractionConceptsKA1 domainMAP/microtubule affinity-regulating kinasesMicrotubule affinity-regulating kinaseGroup of kinasesIntramolecular autoinhibitory interactionAnionic phospholipid bindingAnionic phospholipidsSite-directed mutagenesisAutoinhibitory interactionsRegulatory modulesAutoinhibitory roleProtein modulesMembrane-bound targetsRelated kinasesBind membranesFamily kinasesKinase domainProtein kinasePhospholipid activationC-terminusRegulatory mechanismsPhospholipid bindingMechanistic basisKinaseAutoinhibitory activity