Integrin alpha-IIb cytoplasmic tail – filamin A complex (ITGA2B-FLNA)

The interaction between the Integrin alpha-IIb (ITGA2B) cytoplasmic tail and Filamin A (FLNA) is a critical regulatory node in platelet physiology and thrombus formation. Integrin alpha-IIb, when complexed with integrin beta-3, forms the GPIIb/IIIa receptor, which is the primary mediator of platelet aggregation through its binding to fibrinogen (UniProt P08514). Filamin A is a large actin-binding protein that interacts specifically with the cytoplasmic tail of the alpha-IIb subunit, acting as a scaffold that links the receptor to the actin cytoskeleton and modulates its activation state (UniProt P21333; Kiema et al., 2006). This interaction is a key component of inside-out signaling, which transitions the integrin from a low-affinity to a high-affinity state, and outside-in signaling, which governs post-ligand binding events like platelet spreading and clot retraction (Calderwood, 2004). Because traditional GPIIb/IIIa inhibitors targeting the extracellular domain are often associated with significant bleeding risks and paradoxical platelet activation, the ITGA2B-FLNA interaction has emerged as a novel intracellular therapeutic target. Research focuses on developing small molecules or peptidomimetics that can selectively disrupt this interface to prevent pathological thrombosis with a potentially improved safety profile compared to current antiplatelet therapies (Liu et al., 2015).

Other names

GPIIb-Filamin A interactionIntegrin alpha-IIb/Filamin A bindingCD41-FLNA complexITGA2B-FLNA interaction

Disruption of the protein-protein interaction between the integrin alpha-IIb cytoplasmic tail and filamin A to modulate integrin activation and cytoskeletal linkage.