Andrews R K, López J A, Berndt M C
Hazel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Int J Biochem Cell Biol. 1997 Jan;29(1):91-105. doi: 10.1016/s1357-2725(96)00122-7.
When a blood vessel is injured, control of bleeding starts with the rapid adhesion of circulating platelets to the site of damage. Within seconds, the adhered platelets are activated, secrete the contents of storage organelles, spread out over the damaged area and recruit more platelets to the developing thrombus. However, if this same process occurs in a diseased, sclerotic or occluded vessel, the resulting platelet thrombus may break away and block the coronary artery, causing a heart attack, or restrict blood supply to the brain, causing a stroke. The glycoprotein (GP) Ib-IX-V complex, a member of the leucine-rich protein family, is a constitutive platelet membrane receptor for von Willebrand Factor (vWF), a multimeric adhesive glycoprotein found in the matrix underlying the endothelial cell lining of the blood vessel wall and in the plasma. Binding of vWF to the GP. Ib-IX-V complex regulates adhesion of platelets to the subendothelium at high shear flow, and initiates signal transduction leading to platelet activation. The GP Ib-IX-V complex also constitutes a binding site for alpha-thrombin, an interaction that facilitates thrombin-dependent platelet activation. This review will focus on recent detailed analysis of the GP Ib-IX-V complex and vWF that has identified discrete amino acid sequences that mediate their interaction. An anionic/sulfated tyrosine sequence of the GP Ib alpha-chain that is critical for binding of the GP Ib-IX-V complex to both vWF and alpha-thrombin is analogous to sulfated anionic amino acid sequences mediating interactions of other adhesive proteins, including P-selectin binding to PSGL-1 and Factor VIII binding to vWF.
当血管受损时，止血过程始于循环中的血小板迅速黏附到损伤部位。数秒内，黏附的血小板被激活，分泌储存细胞器的内容物，在损伤区域铺展并募集更多血小板至正在形成的血栓处。然而，如果同样的过程发生在病变、硬化或闭塞的血管中，形成的血小板血栓可能会脱落并阻塞冠状动脉，导致心脏病发作，或限制脑部血液供应，引发中风。糖蛋白（GP）Ib-IX-V复合物是富含亮氨酸蛋白家族的成员，是血管性血友病因子（vWF）的组成型血小板膜受体，vWF是一种多聚体黏附糖蛋白，存在于血管壁内皮细胞内衬下方的基质以及血浆中。vWF与GP Ib-IX-V复合物的结合在高剪切流条件下调节血小板与内皮下的黏附，并启动导致血小板激活的信号转导。GP Ib-IX-V复合物也是α-凝血酶的结合位点，这种相互作用促进凝血酶依赖性血小板激活。本综述将聚焦于对GP Ib-IX-V复合物和vWF的最新详细分析，这些分析确定了介导它们相互作用的离散氨基酸序列。GP Ibα链的一个阴离子/硫酸化酪氨酸序列对于GP Ib-IX-V复合物与vWF和α-凝血酶的结合至关重要，它类似于介导其他黏附蛋白相互作用的硫酸化阴离子氨基酸序列，包括P-选择素与PSGL-1的结合以及因子VIII与vWF的结合。
