STRUCTURAL BIOLOGY OF GLYCOPROTEIN IIB-IIIA

Glycoprotein IIb-IIIa (GPIIb-IIIa), a calcium-dependent heterodimer wh ose expression is restricted to platelets and megakaryocytes, contains a binding site for protein ligands such as fibrinogen and von Willebr and factor (vWf) whose exposure by platelet stimulation is a prerequis ite for platelet aggregation. GPIIb-IIIa heterodimers ave assembled fr om nascent GPIIb and GPIIIa subunits in the calcium-rich environment o f the endoplasmic veticulum, and correctly folded heterodimers ave tra nsported from the endoplasmic reticulum through the Golgi apparatus to the cell surface. Agonist stimulation of platelets produces a conform ational change in GPIIb-IIIa that exposes its ligand binding site, a p rocess termed ''inside-out'' signaling. This signaling process, by int eracting with the cytoplasmic extensions of GPIIb and GPIIIa, converts the heterodimer from an inactive to an activated state capable of bin ding soluble ligands.