grant
Platelet alphaIIbbeta3 activation and its therapeutic targeting
Organization MASSACHUSETTS GENERAL HOSPITALLocation BOSTON, UNITED STATESPosted 1 Sept 2019Deadline 31 May 2029
NIHUS FederalResearch GrantFY2025280 kDa actin-binding proteinAdhesionsAdhesivesAdoptedAffinityAffinity ChromatographyAgonistApoplexyBindingBinding SitesBiochemicalBleedingBlood Coagulation Factor IBlood Coagulation Factor OneBlood Factor OneBlood PlateletsBlood megakaryocyteBrain Vascular AccidentCD61CD61 AntigensCardiac infarctionCell Communication and SignalingCell SignalingCell membraneCerebral StrokeCerebrovascular ApoplexyCerebrovascular StrokeChargeCirculationClot retractionCoagulation Factor ICoagulation Factor OneCombining SiteContracting OpportunitiesContractsCryo-electron MicroscopyCryoelectron MicroscopyCytoplasmic DomainCytoplasmic MembraneCytoplasmic TailDataDevelopmentDiseaseDisorderDrugsElectron CryomicroscopyEngineeringEnvironmentEvaluationExhibitsExposure toF-ActinFactor IFactor OneFibrinFibrinogenFilamentous ActinFundingGP IIIaGP3AGPIIIaGoalsGrantHeadHealthHemorrhageHemostasisHemostatic AgentsHemostatic functionHemostaticsITGB3ITGB3 geneIntegrin Beta 3Integrin beta3Integrin β3IntegrinsIntegrins Extracellular MatrixIntracellular Communication and SignalingK562 CellsLegLengthLigand BindingLigandsLinkMarrow plateletMeasuresMedicationMegakaryocytesMegalokaryocyteMembraneMiceMice MammalsModelingMolecular ConfigurationMolecular ConformationMolecular InteractionMolecular StereochemistryMurineMusMyocardial InfarctMyocardial InfarctionNAITNatureOralPTP genePathologicPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPharmaceutical PreparationsPhysiologicPhysiologicalPlasma MembranePlatelet Fibrinogen Receptor, Beta SubunitPlatelet GPIIIaPlatelet Glycoprotein IIIaPlatelet Membrane Glycoprotein IIIaPlatelet aggregationPlateletsPlayProcessPropertyProteinsProtocolProtocols documentationReactive SiteReceptor ActivationReceptor ProteinRegulationReportingResolutionRestRoleSeriesSideSignal TransductionSignal Transduction SystemsSignalingSiteStrokeStructureTM DomainTestingThrombaseThrombinThrombocytesThrombosisTransmembrane DomainTransmembrane Regionaffinity purificationantagonismantagonistbiological signal transductionblood lossbrain attackcardiac infarctcerebral vascular accidentcerebrovascular accidentconfocal imagingconformationconformationalconformational stateconformationallyconformationscoronary attackcoronary infarctcoronary infarctioncryo-EMcryoEMcryogenic electron microscopydensitydevelopmentaldrug/agentfibrinogenasefilaminfilamin 1filamin Aflexibilityflexibleheart attackheart infarctheart infarctioniPSiPSCiPSCsinduced pluripotent cellinduced pluripotent stem cellinducible pluripotent cellinducible pluripotent stem cellinhibitorinjury to the vasculatureinsightmembrane structuremimeticsmutantnano particlenano-sized particlenanoparticlenanosized particlenovelpatient oriented outcomespeptide mimeticpeptide mimicpeptidomimeticsplasmalemmapreservationpreventpreventingprotein purificationreceptorresolutionsresponsesealsmall moleculesocial rolestrokedstrokessuccesstherapeutic targetthrombotic diseasethrombotic disordervascular injury
Description preview
Abstract
Platelet integrin αIIbβ3 plays a central and nonredundant role in hemostasis and thrombosis. It is normally kept
in a default inactive conformation in resting free-flowing platelets in the circulation. Despite extensive efforts, it
remains unclear how αIIbβ3 is normally kept inactive in the native membrane environment of circulation…
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