2018
Structural basis of the filamin A actin-binding domain interaction with F-actin
Iwamoto DV, Huehn A, Simon B, Huet-Calderwood C, Baldassarre M, Sindelar CV, Calderwood DA. Structural basis of the filamin A actin-binding domain interaction with F-actin. Nature Structural & Molecular Biology 2018, 25: 918-927. PMID: 30224736, PMCID: PMC6173970, DOI: 10.1038/s41594-018-0128-3.Peer-Reviewed Original ResearchMeSH KeywordsActinsCryoelectron MicroscopyFilaminsHumansModels, MolecularMutation, MissenseProtein DomainsConceptsActin-binding domainCalponin homology domainHomology domainF-actinActin cross-linking proteinFunction mutationsTandem calponin homology domainsDisease-associated mutantsCryo-electron microscopyHigh-resolution structuresNumerous genetic diseasesSequence conservationHigher-order structureLinking proteinStructural basisDomain interactionsCell shapeActin filamentsMolecular understandingN-terminalFunctional studiesGenetic diseasesMissense mutationsMutationsAtomic resolution
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 effectorsPurification and SAXS Analysis of the Integrin Linked Kinase, PINCH, Parvin (IPP) Heterotrimeric Complex
Stiegler AL, Grant TD, Luft JR, Calderwood DA, Snell EH, Boggon TJ. Purification and SAXS Analysis of the Integrin Linked Kinase, PINCH, Parvin (IPP) Heterotrimeric Complex. PLOS ONE 2013, 8: e55591. PMID: 23383235, PMCID: PMC3561323, DOI: 10.1371/journal.pone.0055591.Peer-Reviewed Original ResearchConceptsIPP complexEnsemble optimization methodDetailed purification protocolHeterotrimeric protein complexIntegrin Linked KinaseIntegrin adhesion receptorsInter-domain linkerInter-domain interactionsInter-domain contactsGel filtration analysisΑ-parvinLIM1 domainHuman ILKSmall-angle X-ray scatteringHeterotrimeric complexProtein complexesFocal adhesionsAdhesion receptorsPINCH proteinFirst structural characterizationFiltration analysisPurification protocolConformational restraintsKinaseILKMechanism 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 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
2010
Structure of a double ubiquitin‐like domain in the talin head: a role in integrin activation
Goult BT, Bouaouina M, Elliott PR, Bate N, Patel B, Gingras AR, Grossmann JG, Roberts GC, Calderwood DA, Critchley DR, Barsukov IL. Structure of a double ubiquitin‐like domain in the talin head: a role in integrin activation. The EMBO Journal 2010, 29: 1069-1080. PMID: 20150896, PMCID: PMC2845276, DOI: 10.1038/emboj.2010.4.Peer-Reviewed Original Research
2009
Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase
Chiswell BP, Stiegler AL, Razinia Z, Nalibotski E, Boggon TJ, Calderwood DA. Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase. Journal Of Structural Biology 2009, 170: 157-163. PMID: 19963065, PMCID: PMC2841223, DOI: 10.1016/j.jsb.2009.12.002.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnkyrin RepeatBinding, CompetitiveCrystallizationDNA-Binding ProteinsGene Expression RegulationLIM Domain ProteinsMembrane ProteinsModels, MolecularMolecular Sequence DataMutagenesisProtein BindingProtein Serine-Threonine KinasesSignal TransductionConceptsIntegrin-linked kinaseAnkyrin repeat domainLIM1 domainIPP complexIsoform-specific functionsIntegrin adhesion receptorsDifferent cellular responsesPINCH2Repeat domainPINCH1Point mutagenesisStructural basisAdhesion receptorsCellular responsesAlters localizationDifferential regulationSame binding siteDirect competitionBinding sitesKinaseDomainAnkyrinParvinMutagenesisMammalsThe Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation
Goult BT, Bouaouina M, Harburger DS, Bate N, Patel B, Anthis NJ, Campbell ID, Calderwood DA, Barsukov IL, Roberts GC, Critchley DR. The Structure of the N-Terminus of Kindlin-1: A Domain Important for αIIbβ3 Integrin Activation. Journal Of Molecular Biology 2009, 394: 944-956. PMID: 19804783, PMCID: PMC2963925, DOI: 10.1016/j.jmb.2009.09.061.Peer-Reviewed Original Research
2008
Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin β Tails*
Lad Y, Jiang P, Ruskamo S, Harburger DS, Ylänne J, Campbell ID, Calderwood DA. Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin β Tails*. Journal Of Biological Chemistry 2008, 283: 35154-35163. PMID: 18829455, PMCID: PMC2596399, DOI: 10.1074/jbc.m802592200.Peer-Reviewed Original ResearchConceptsCell-extracellular matrix adhesion sitesHuman filaminN-terminal actin-binding domainProtein-protein interaction studiesActin cross-linking protein filaminIntegrin β tailsMatrix adhesion sitesActin-binding domainIntegrin beta tailsN-terminal portionIntegrin-cytoskeleton linkagesImmunoglobulin-like domainsIntegrin tailsΒ tailAdaptor proteinMigfilinBeta tailsProtein filaminCommon binding siteMolecular basisStructural basisAdhesion sitesCell shapeFilaminCell adhesion
2007
Structure of three tandem filamin domains reveals auto‐inhibition of ligand binding
Lad Y, Kiema T, Jiang P, Pentikäinen OT, Coles CH, Campbell ID, Calderwood DA, Ylänne J. Structure of three tandem filamin domains reveals auto‐inhibition of ligand binding. The EMBO Journal 2007, 26: 3993-4004. PMID: 17690686, PMCID: PMC1948075, DOI: 10.1038/sj.emboj.7601827.Peer-Reviewed Original Research
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
The Kindler Syndrome Protein Is Regulated by Transforming Growth Factor-β and Involved in Integrin-mediated Adhesion*
Kloeker S, Major MB, Calderwood DA, Ginsberg MH, Jones DA, Beckerle MC. The Kindler Syndrome Protein Is Regulated by Transforming Growth Factor-β and Involved in Integrin-mediated Adhesion*. Journal Of Biological Chemistry 2003, 279: 6824-6833. PMID: 14634021, DOI: 10.1074/jbc.m307978200.Peer-Reviewed Original ResearchMeSH KeywordsActinsAmino Acid SequenceBlotting, NorthernBlotting, WesternCell AdhesionCell LineCell MovementCytoplasmCytoskeletonDisease ProgressionDNA, ComplementaryExtracellular Matrix ProteinsFluorescent Antibody Technique, IndirectGene Expression RegulationHumansIntegrin beta1Integrin beta3IntegrinsMembrane ProteinsModels, MolecularMolecular Sequence DataMutationNeoplasm ProteinsOligonucleotide Array Sequence AnalysisProtein BindingProtein Structure, TertiaryRNARNA, MessengerRNA, Small InterferingSequence Homology, Amino AcidTime FactorsTransfectionTransforming Growth Factor betaUp-RegulationConceptsHuman mammary epithelial cellsCytoplasmic domainIntegrin cytoplasmic domainBeta3 integrin cytoplasmic domainsCDNA microarray analysisTGF-beta stimulationNormal cell spreadingMammary epithelial cellsSyndrome proteinFERM domainFocal adhesionsTranscriptional profilesProtein abundanceCritical residuesMicroarray analysisCell spreadingGene leadTalin-FERMCell migrationCancer progressionIntegrin betaGenesCell processesAutosomal recessive genodermatosisEpithelial cellsIntegrin β cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling
Calderwood DA, Fujioka Y, de Pereda JM, García-Alvarez B, Nakamoto T, Margolis B, McGlade CJ, Liddington RC, Ginsberg MH. Integrin β cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 2272-2277. PMID: 12606711, PMCID: PMC151330, DOI: 10.1073/pnas.262791999.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAnimalsCHO CellsCricetinaeCytoplasmDatabases as TopicDNADose-Response Relationship, DrugElectrophoresis, Polyacrylamide GelGlutathione TransferaseHumansIntegrin beta ChainsIntegrinsMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedMutationPhosphorylationPhosphotyrosinePrecipitin TestsProtein BindingProtein ConformationProtein Structure, TertiaryRecombinant Fusion ProteinsRecombinant ProteinsSequence Homology, Amino AcidSignal TransductionTransfectionTyrosineConceptsIntegrin beta tailsBeta tailsPTB domainIntegrin tailsDok-1Heterodimeric integrin adhesion receptorsBiological functionsDomain interactionsPTB domain-containing proteinsDomain-containing proteinsDomain-ligand interactionsPhosphotyrosine-binding (PTB) domainPhosphotyrosine-binding domainCytoplasmic domain interactionsIntegrin-binding proteinsIntegrin adhesion receptorsIntegrin alpha IIbNPXY motifProtein modulesCytoplasmic domainCytoplasmic proteinsAlpha IIbCytoskeletal proteinsCanonical recognition sequenceInteracting residuesStructural 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
2002
The Phosphotyrosine Binding-like Domain of Talin Activates Integrins*
Calderwood DA, Yan B, de Pereda JM, Alvarez B, Fujioka Y, Liddington RC, Ginsberg MH. The Phosphotyrosine Binding-like Domain of Talin Activates Integrins*. Journal Of Biological Chemistry 2002, 277: 21749-21758. PMID: 11932255, DOI: 10.1074/jbc.m111996200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsCell AdhesionCell SeparationCHO CellsCricetinaeCytoplasmDNA, ComplementaryFlow CytometryIntegrinsKineticsLigandsModels, MolecularMolecular Sequence DataMutationPhosphotyrosineProtein BindingProtein FoldingProtein Structure, TertiaryRecombinant Fusion ProteinsRecombinant ProteinsSequence Homology, Amino AcidSurface Plasmon ResonanceTalinTime FactorsConceptsIntegrin beta cytoplasmic domainsBeta cytoplasmic domainsIntegrin beta tailsPTB domainCytoplasmic domainBeta tailsHead domainBeta3 tailPhosphotyrosine-binding (PTB) domainIntegrin adhesion receptorsBeta turnActivation of integrinsBinding-like domainsNPXY motifFERM domainTalin fragmentCellular regulationF3 subdomainsActivates IntegrinPeptide ligandsIntegrin activationAdhesion receptorsTalinMotifIntegrins