Integrin beta-3 cytoplasmic tail – talin-1 head domain complex (ITGB3-TLN1 complex)

The interaction between the Integrin beta-3 (ITGB3) cytoplasmic tail and the Talin-1 head domain (THD) is a fundamental regulatory mechanism for integrin activation, particularly in platelets [Source: UniProt P05106, Q9Y490]. This "inside-out" signaling event occurs when the F3 subdomain of the talin head binds to the membrane-proximal NPxY motif of the integrin beta-3 tail, disrupting the inhibitory interaction between the alpha and beta subunits [Source: PubMed 17512409]. This disruption triggers a conformational change that extends the extracellular domain of the integrin, significantly increasing its affinity for ligands such as fibrinogen and von Willebrand factor [Source: PubMed 22307322]. Because this step is essential for platelet aggregation and thrombus formation, it is a critical driver of cardiovascular pathologies like myocardial infarction and stroke [Source: PubMed 24652458]. While most current anti-platelet drugs target the extracellular ligand-binding site, the ITGB3-THD interaction is an emerging therapeutic target for intracellular inhibitors [Source: PubMed 21908603]. Experimental agents like the peptidomimetic mP6 have demonstrated that blocking this specific protein-protein interaction can inhibit thrombosis with a potentially improved safety profile regarding bleeding risks [Source: PubMed 21908603].

Other names

Integrin beta-3/Talin-1 interactionITGB3-THD complexIntegrin activation complexGPIIIa-Talin interaction

Competitive inhibition of the talin-integrin interaction, preventing the conformational change required for high-affinity ligand binding (integrin activation).