Model for the main final steps in talin-1–dependent platelet integrin activation. (A) Talin-1 is autoinhibited where the F3 integrin–binding site (red disc) is obscured by its interaction with the R9 helical bundle, and the PI(4,5)P₂ binding site in F2 and F3 are masked by the R12 helical bundle. (B) The Rap1-binding sites in F0 and F1 were not part of the autoinhibited structure and therefore available to bind Rap1-GTP.¹⁸  (C) At the membrane, PI(4,5)P₂ can disrupt the F3–R9 and F2–R12 interactions to unveil the talin-1 F3 integrin–binding site (red disc). (D) The binding of talin-1 F3 domain to the integrin β tail induces activation of αIIbβ3 and β1 integrins.