2022
Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry
Simon B, Lou HJ, Huet-Calderwood C, Shi G, Boggon TJ, Turk BE, Calderwood DA. Tousled-like kinase 2 targets ASF1 histone chaperones through client mimicry. Nature Communications 2022, 13: 749. PMID: 35136069, PMCID: PMC8826447, DOI: 10.1038/s41467-022-28427-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceCatalytic DomainCell Cycle ProteinsConserved SequenceCrystallography, X-RayHistonesHumansMolecular ChaperonesMolecular Docking SimulationMolecular MimicryMutagenesisPeptide LibraryPhosphorylationProtein KinasesRecombinant ProteinsSubstrate SpecificityConceptsTousled-like kinaseDNA replication-coupled nucleosome assemblyNuclear serine-threonine kinaseReplication-coupled nucleosome assemblyHistone chaperone proteinsGlobular N-terminal domainProper cell divisionPhosphorylation site motifsSerine-threonine kinaseShort sequence motifsAsf1 histone chaperonesC-terminal tailN-terminal domainHistone chaperonesGenome maintenanceNucleosome assemblySequence motifsChaperone proteinsNon-catalytic interactionsCatalytic domainCell divisionSite motifN-terminusStringent selectivityCell growth
2015
CCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation
Draheim KM, Li X, Zhang R, Fisher OS, Villari G, Boggon TJ, Calderwood DA. CCM2–CCM3 interaction stabilizes their protein expression and permits endothelial network formation. Journal Of Cell Biology 2015, 208: 987-1001. PMID: 25825518, PMCID: PMC4384732, DOI: 10.1083/jcb.201407129.Peer-Reviewed Original ResearchMeSH KeywordsApoptosis Regulatory ProteinsBinding SitesCarrier ProteinsCell LineCell ProliferationCentral Nervous SystemCrystallography, X-RayGene ExpressionHemangioma, Cavernous, Central Nervous SystemHumansMembrane ProteinsMutagenesisNeovascularization, PhysiologicPaxillinProtein BindingProtein Interaction MappingProtein Structure, TertiaryProteolysisProto-Oncogene ProteinsRNA InterferenceRNA, Small InterferingSequence AlignmentConceptsBinding-deficient mutantStructure-guided mutagenesisNormal cell growthCerebral cavernous malformationsEndothelial network formationHomology domainCCM3 proteinsProteasomal degradationEndothelial cell network formationMolecular basisCell network formationEssential adaptorCell growthFunctional significanceCCM3 expressionX-ray crystallographyProtein expressionCCM2CCM3Network formationExpressionMutantsHP1MutagenesisAdaptor
2013
Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6
Gao J, Ha BH, Lou HJ, Morse EM, Zhang R, Calderwood DA, Turk BE, Boggon TJ. Substrate and Inhibitor Specificity of the Type II p21-Activated Kinase, PAK6. PLOS ONE 2013, 8: e77818. PMID: 24204982, PMCID: PMC3810134, DOI: 10.1371/journal.pone.0077818.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCatalytic DomainCrystallizationCrystallography, X-RayHEK293 CellsHumansIndolesModels, MolecularMolecular Sequence DataP21-Activated KinasesPeptide FragmentsPhosphorylationProtein ConformationPyrazolesPyrrolesSequence Homology, Amino AcidSignal TransductionSubstrate SpecificitySunitinibConceptsP21-activated kinaseCo-crystal structureRho family small GTPasesPeptide substrate specificityATP-competitive inhibitorsStructure-function relationshipsSmall GTPasesPAK familyCatalytic domainMelanoma-associated mutationsSubstrate specificityInhibitor specificityPAK6Receptor signalingPF-3758309Important effectorsMechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation
Liu W, Draheim KM, Zhang R, Calderwood DA, Boggon TJ. Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation. Molecular Cell 2013, 49: 719-729. PMID: 23317506, PMCID: PMC3684052, DOI: 10.1016/j.molcel.2012.12.005.Peer-Reviewed Original ResearchAdaptor Proteins, Signal TransducingAmino Acid MotifsAmino Acid SequenceCell Line, TumorConserved SequenceCrystallography, X-RayHumansHydrogen BondingHydrophobic and Hydrophilic InteractionsIntegrin beta1Intracellular Signaling Peptides and ProteinsKRIT1 ProteinMembrane ProteinsMicrotubule-Associated ProteinsModels, MolecularMolecular Sequence DataProtein BindingProtein Interaction Domains and MotifsProtein Structure, QuaternaryProto-Oncogene ProteinsSignal Transduction
2012
Structural and Functional Characterization of the Kindlin-1 Pleckstrin Homology Domain*
Yates LA, Lumb CN, Brahme NN, Zalyte R, Bird LE, De Colibus L, Owens RJ, Calderwood DA, Sansom MS, Gilbert RJ. Structural and Functional Characterization of the Kindlin-1 Pleckstrin Homology Domain*. Journal Of Biological Chemistry 2012, 287: 43246-43261. PMID: 23132860, PMCID: PMC3527912, DOI: 10.1074/jbc.m112.422089.Peer-Reviewed Original ResearchStructural Basis for Paxillin Binding and Focal Adhesion Targeting of β-Parvin*
Stiegler AL, Draheim KM, Li X, Chayen NE, Calderwood DA, Boggon TJ. Structural Basis for Paxillin Binding and Focal Adhesion Targeting of β-Parvin*. Journal Of Biological Chemistry 2012, 287: 32566-32577. PMID: 22869380, PMCID: PMC3463362, DOI: 10.1074/jbc.m112.367342.Peer-Reviewed Original ResearchConceptsΒ-parvinFocal adhesionsPaxillin bindingΑ-parvinFocal adhesion targetingN-terminal α-helixPaxillin LD1 motifCalponin homology domainFirst molecular detailsHigh sequence similarityCytoplasmic adaptor proteinIntegrin-linked kinasePaxillin LD1Co-crystal structureLD4 motifSignificant conformational flexibilityHomology domainAdaptor proteinCellular functionsSequence similarityRepeat motifsProper localizationMolecular detailsPaxillinStructural basisStructural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1)
Li X, Zhang R, Draheim KM, Liu W, Calderwood DA, Boggon TJ. Structural Basis for Small G Protein Effector Interaction of Ras-related Protein 1 (Rap1) and Adaptor Protein Krev Interaction Trapped 1 (KRIT1). Journal Of Biological Chemistry 2012, 287: 22317-22327. PMID: 22577140, PMCID: PMC3381192, DOI: 10.1074/jbc.m112.361295.Peer-Reviewed Original ResearchAmino Acid SequenceCrystallography, X-RayGene Expression RegulationGTP PhosphohydrolasesHemangioma, Cavernous, Central Nervous SystemHumansIntegrinsKRIT1 ProteinMicrotubule-Associated ProteinsModels, BiologicalModels, MolecularMolecular Sequence DataMutagenesisPoint MutationProtein ConformationProtein Interaction MappingProtein Structure, TertiaryProto-Oncogene ProteinsRap1 GTP-Binding ProteinsSequence Homology, Amino AcidSignal Transduction
2008
The structural basis of integrin-linked kinase–PINCH interactions
Chiswell BP, Zhang R, Murphy JW, Boggon TJ, Calderwood DA. The structural basis of integrin-linked kinase–PINCH interactions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 20677-20682. PMID: 19074270, PMCID: PMC2634877, DOI: 10.1073/pnas.0811415106.Peer-Reviewed Original ResearchConceptsIntegrin-linked kinaseLIM1 domainGrowth factor signalingAtomic resolution descriptionILK bindingAnkyrin repeatsILK-PINCHHeterotrimeric complexZinc fingerMolecular basisMutagenesis dataStructural basisCell adhesionPoint mutationsConformational flexibilityKey interactionsParvinConvergence pointLim1DomainAnkyrinKinaseComplexesRepeatsSignaling
2006
The Molecular Basis of Filamin Binding to Integrins and Competition with Talin
Kiema T, Lad Y, Jiang P, Oxley CL, Baldassarre M, Wegener KL, Campbell ID, Ylänne J, Calderwood DA. The Molecular Basis of Filamin Binding to Integrins and Competition with Talin. Molecular Cell 2006, 21: 337-347. PMID: 16455489, DOI: 10.1016/j.molcel.2006.01.011.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesCalpainContractile ProteinsCrystallography, X-RayFilaminsIntegrin beta ChainsMiceMicrofilament ProteinsModels, MolecularMolecular Sequence DataNIH 3T3 CellsNuclear Magnetic Resonance, BiomolecularProtein BindingProtein ConformationProtein Structure, TertiaryRecombinant Fusion ProteinsReproducibility of ResultsSequence Homology, Amino AcidTalinConceptsAdhesion receptorsTalin-dependent integrin activationActin-crosslinking proteinsIntegrin adhesion receptorsHigh-resolution structuresFilamin bindingExtended beta strandActin cytoskeletonIntegrin tailsMultiple transmembraneMolecular basisStrands CBeta strandsDomain interactionsBiochemical signalsIntegrin functionIntegrin activationFilamin ATalinCell membraneTail formsCytoskeletonProteinBinding sitesFilamin
2003
Structural Determinants of Integrin Recognition by Talin
Garcı́a-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC. Structural Determinants of Integrin Recognition by Talin. Molecular Cell 2003, 11: 49-58. PMID: 12535520, DOI: 10.1016/s1097-2765(02)00823-7.Peer-Reviewed Original ResearchConceptsBidirectional signal transductionFragment of talinIntegrin adhesion receptorsFERM domainIntegrin tailsCytoplasmic domainCytoplasmic proteinsSignal transductionIntegrin linkagesTransmembrane receptorsTalinMutational analysisAdhesion receptorsDomain recognitionCell interiorIntegrin recognitionStructural determinantsLigand interactionsNovel variantsStructural paradigmFragmentsTransductionReceptorsTailDomain