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 ResearchConceptsActin-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
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 formationExpressionMutantsHP1MutagenesisAdaptorDirect Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*
Simpson MA, Bradley WD, Harburger D, Parsons M, Calderwood DA, Koleske AJ. Direct Interactions with the Integrin β1 Cytoplasmic Tail Activate the Abl2/Arg Kinase*. Journal Of Biological Chemistry 2015, 290: 8360-8372. PMID: 25694433, PMCID: PMC4375489, DOI: 10.1074/jbc.m115.638874.Peer-Reviewed Original ResearchConceptsIntegrin β1 cytoplasmic tailExtracellular matrix adhesion receptorsSrc homology domainFibroblast cell motilityIntegrin β1Β1 cytoplasmic tailMembrane-proximal segmentAdhesion complex formationMatrix adhesion receptorsNonreceptor tyrosine kinaseArg kinase activityArg nonreceptor tyrosine kinaseCancer cell invasivenessHomology domainActin cytoskeletonCytoplasmic tailCytoskeletal remodelingDendrite morphogenesisTyr-783Kinase domainPhosphorylated regionAbl familyΒ1 tailArg kinaseCell motility
2012
Structural 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 basis