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
2014
The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering
Ellis SJ, Lostchuck E, Goult BT, Bouaouina M, Fairchild MJ, López-Ceballos P, Calderwood DA, Tanentzapf G. The Talin Head Domain Reinforces Integrin-Mediated Adhesion by Promoting Adhesion Complex Stability and Clustering. PLOS Genetics 2014, 10: e1004756. PMID: 25393120, PMCID: PMC4230843, DOI: 10.1371/journal.pgen.1004756.Peer-Reviewed Original Research
2013
Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*
Brahme NN, Harburger DS, Kemp-O'Brien K, Stewart R, Raghavan S, Parsons M, Calderwood DA. Kindlin Binds Migfilin Tandem LIM Domains and Regulates Migfilin Focal Adhesion Localization and Recruitment Dynamics*. Journal Of Biological Chemistry 2013, 288: 35604-35616. PMID: 24165133, PMCID: PMC3853305, DOI: 10.1074/jbc.m113.483016.Peer-Reviewed Original ResearchConceptsFocal adhesionsLIM domainsActin cytoskeletonFluorescence resonance energy transferFA localizationActin-rich stress fibersC-terminal LIM domainsLIM domain regionTandem LIM domainsTwo-hybrid screenDomain-containing adaptor proteinFocal adhesion localizationIntegrin-binding proteinsIntegrin adhesion receptorsPulldown assaysAdaptor proteinMigfilinFA formationKindlinRecruitment dynamicsStress fibersKindlin-2Integrin activationIntracellular proteinsAdhesion receptorsASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain*
Razinia Z, Baldassarre M, Cantelli G, Calderwood DA. ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain*. Journal Of Biological Chemistry 2013, 288: 32093-32105. PMID: 24052262, PMCID: PMC3814802, DOI: 10.1074/jbc.m113.496604.Peer-Reviewed Original ResearchConceptsHematopoietic cell differentiationSpecificity subunitProteasomal degradationF-actin-rich structuresE3 ubiquitin ligase complexCell differentiationNormal subcellular localizationHomology 1 domainLoss of filaminUbiquitin acceptor sitesActin-binding domainCross-linking proteinsActin-binding siteLigase complexActin cytoskeletonTransmembrane proteinSubcellular localizationΑ-actinin1Transient expressionASB2αDegradation of filaminMinimal fragmentLysine residuesFilaminCell adhesion
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 TransductionFilamins in Mechanosensing and Signaling
Razinia Z, Mäkelä T, Ylänne J, Calderwood DA. Filamins in Mechanosensing and Signaling. Annual Review Of Biophysics 2012, 41: 227-246. PMID: 22404683, PMCID: PMC5508560, DOI: 10.1146/annurev-biophys-050511-102252.Peer-Reviewed Original ResearchConceptsPlasma membraneActin filamentsActin-binding proteinsExtracellular matrix connectionsCortical rigidityActin cytoskeletonCellular functionsCell cortexTranscription factorsTransmembrane receptorsAdhesion proteinsCell shapeFilaminIon channelsDiverse arrayFunctional evidenceEssential roleProteinMatrix connectionsPhysical forcesMembraneFilamentsCytoskeletalMechanosensingCytoskeletonA Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*
Bouaouina M, Goult BT, Huet-Calderwood C, Bate N, Brahme NN, Barsukov IL, Critchley DR, Calderwood DA. A Conserved Lipid-binding Loop in the Kindlin FERM F1 Domain Is Required for Kindlin-mediated αIIbβ3 Integrin Coactivation*. Journal Of Biological Chemistry 2012, 287: 6979-6990. PMID: 22235127, PMCID: PMC3293583, DOI: 10.1074/jbc.m111.330845.Peer-Reviewed Original ResearchConceptsIntegrin β tailsTalin FERM domainFERM domainFocal adhesionsΒ tailTalin headHeterodimeric integrin adhesion receptorsIntegrin activationKindlin-1Membrane-binding motifFERM domain proteinsIntegrin β subunitsShort cytoplasmic tailAcidic membrane phospholipidsIntegrin adhesion receptorsΑIIbβ3 integrin activationDomain proteinsIntegrin tailsCytoplasmic domainCytoplasmic tailKindlinKindlin familyDomain interactionsPhospholipid head groupsPolylysine motifFilamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells
Baldassarre M, Razinia Z, Brahme NN, Buccione R, Calderwood DA. Filamin A controls matrix metalloproteinase activity and regulates cell invasion in human fibrosarcoma cells. Journal Of Cell Science 2012, 125: 3858-3869. PMID: 22595522, PMCID: PMC3462082, DOI: 10.1242/jcs.104018.Peer-Reviewed Original ResearchMeSH KeywordsActinsCell AdhesionCell Line, TumorCell MovementContractile ProteinsEnzyme ActivationExtracellular MatrixFibrosarcomaFilaminsGene Knockdown TechniquesHumansIntegrinsMatrix Metalloproteinase 14Matrix Metalloproteinase 2Microfilament ProteinsNeoplasm InvasivenessPhenotypeProtein Structure, TertiaryConceptsFilamin AActin cytoskeletonCell invasionActin-binding domainCell surface adhesion proteinsControls cell motilityActin-binding proteinsIntegrin adhesion receptorsRandom cell migrationAbility of cellsArray of intracellularBreast cancer lossSurface adhesion proteinsHuman fibrosarcoma cellsExtracellular matrix degradationMatrix metalloproteinase activityFilamin expressionKnockdown cellsAdhesion proteinsCell motilityMetalloproteinase activityActin filamentsAdhesion receptorsFilaminECM remodeling
2011
Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells*
Lamsoul I, Burande CF, Razinia Z, Houles TC, Menoret D, Baldassarre M, Erard M, Moog-Lutz C, Calderwood DA, Lutz PG. Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells*. Journal Of Biological Chemistry 2011, 286: 30571-30581. PMID: 21737450, PMCID: PMC3162417, DOI: 10.1074/jbc.m111.220921.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid MotifsAnimalsCarrier ProteinsCell AdhesionFibronectinsGene Expression RegulationHeLa CellsHematopoietic Stem CellsHumansIntegrinsMiceMusclesNIH 3T3 CellsProtein BindingProtein Structure, TertiarySubstrate SpecificitySuppressor of Cytokine Signaling ProteinsConceptsN-terminal regionHematopoietic cellsE3 ubiquitin ligase complexE3 ubiquitin ligase functionShort N-terminal regionUbiquitin ligase complexUbiquitin ligase functionAcid-responsive genesIntegrin-dependent adhesionRetinoic acid-responsive geneCell fateLigase complexSpecificity subunitLigase functionResponsive genesLeukemia cellsProteasomal degradationNovel regulatorFilamin A.Myogenic differentiationStructural insightsASB2αΒ-integrinAcute promyelocytic leukemia cellsStructural homologyKindlins
Bouaouina M, Calderwood DA. Kindlins. Current Biology 2011, 21: r99-r101. PMID: 21300280, DOI: 10.1016/j.cub.2010.12.002.Peer-Reviewed Original Research
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
The 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 ResearchKindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*
Harburger DS, Bouaouina M, Calderwood DA. Kindlin-1 and -2 Directly Bind the C-terminal Region of β Integrin Cytoplasmic Tails and Exert Integrin-specific Activation Effects*. Journal Of Biological Chemistry 2009, 284: 11485-11497. PMID: 19240021, PMCID: PMC2670154, DOI: 10.1074/jbc.m809233200.Peer-Reviewed Original Research
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
2007
The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*
Bouaouina M, Lad Y, Calderwood DA. The N-terminal Domains of Talin Cooperate with the Phosphotyrosine Binding-like Domain to Activate β1 and β3 Integrins*. Journal Of Biological Chemistry 2007, 283: 6118-6125. PMID: 18165225, DOI: 10.1074/jbc.m709527200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell AdhesionCytoskeletal ProteinsIntegrin beta1Integrin beta3MiceProtein Structure, TertiarySignal TransductionTalinStructure 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 ResearchContractile ProteinsFilaminsHumansIntegrinsLigandsMicrofilament ProteinsModels, MolecularProtein BindingProtein Structure, Tertiary
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
2004
Talin controls integrin activation
Calderwood DA. Talin controls integrin activation. Biochemical Society Transactions 2004, 32: 434-437. PMID: 15157154, DOI: 10.1042/bst0320434.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCell AdhesionCytoplasmCytoskeletonHumansIntegrinsLigandsProtein BindingProtein ConformationProtein Structure, TertiaryRNA InterferenceSignal TransductionTalinConceptsIntegrin beta tailsIntegrin activationCytoplasmic domainBeta tailsMajor actin-binding proteinIntegrin beta cytoplasmic domainsBeta cytoplasmic domainsIntegrin cytoplasmic domainIntegrin activation pathwaysCytoskeletal protein talinIntegrin extracellular domainActin-binding proteinsIntegrin adhesion receptorsBinding of talinTalin FERM domainIntegrin-binding siteMulticellular organismsPTB domainFERM domainProtein talinExtracellular ligandsTalin expressionRNA interferenceTalinIntracellular signals