Clemetson K J, Clemetson J M
Theodor Kocher Institute, University of Berne, Switzerland.
Semin Thromb Hemost. 1995;21(2):130-6. doi: 10.1055/s-2007-1000387.
In the early phase of primary hemostasis, platelets adhere to damaged vessel wall by binding via the platelet glycoprotein (GP) Ib-V-IX complex to von Willebrand factor (vWf) exposed on the subendothelium. The complex is composed of four glycoprotein subunits, GPIb alpha, GPIb beta, GPIX and GPV, each with a variable number of leucine-rich repeats. GPIb alpha and GPIb beta are linked by a disulphide bridge while GPIX and GPV associate noncovalently with the complex. The study of defects in the expression of the GPIb-V-IX complex at the platelet surface leading to pathological disorders, like Bernard-Soulier syndrome (BSS), or in the affinity of platelets for vWf, like pseudo-von Willebrand disease, has helped to delineate the binding site for vWf on GPIb alpha. However, the mechanism by which the complex binds to vWf has not yet been elucidated but it must involve changes in the conformation of the molecules as no interaction between platelets and vWf occurs in the plasma. The GPIb-V-IX complex has a binding site for thrombin on GPIb alpha which participates in the platelet activation by that agonist. GPV is also cleaved by thrombin but the function of this proteolysis is not clear. The platelet response to thrombin is slower and weaker when the thrombin binding site on GPIb alpha is blocked or cleaved or when the GPIb-V-IX complex is not expressed on the platelet surface as in classic BSS. At low doses of thrombin, the rapid activation of the platelets via the seven-transmembrane thrombin receptor is dependent on the presence of the GPIb-V-IX complex.
在初级止血的早期阶段，血小板通过血小板糖蛋白（GP）Ib-V-IX复合物与暴露于内皮下的血管性血友病因子（vWf）结合，从而黏附于受损的血管壁。该复合物由四个糖蛋白亚基组成，即GPIbα、GPIbβ、GPIX和GPV，每个亚基都有可变数量的富含亮氨酸的重复序列。GPIbα和GPIbβ通过二硫键相连，而GPIX和GPV则以非共价方式与该复合物结合。对血小板表面GPIb-V-IX复合物表达缺陷导致的病理紊乱（如伯纳德-索利尔综合征（BSS））或血小板对vWf亲和力缺陷（如假性血管性血友病）的研究，有助于明确vWf在GPIbα上的结合位点。然而，该复合物与vWf结合的机制尚未阐明，但这肯定涉及分子构象的变化，因为血小板与vWf在血浆中不发生相互作用。GPIb-V-IX复合物在GPIbα上有一个凝血酶结合位点，该位点参与了该激动剂引起的血小板激活。GPV也会被凝血酶切割，但这种蛋白水解的功能尚不清楚。当GPIbα上的凝血酶结合位点被阻断或切割，或者当血小板表面不表达GPIb-V-IX复合物（如经典BSS）时，血小板对凝血酶的反应会更慢且更弱。在低剂量凝血酶作用下，通过七跨膜凝血酶受体快速激活血小板依赖于GPIb-V-IX复合物的存在。
