Human von Willebrand factor: the molecular glue of platelet plugs.
Human von Willebrand factor: the molecular glue of platelet plugs.
复制标题
人类血管性血友病因子：血小板栓塞的分子胶。
DOI：
10.1016/0968-0004(88)90048-5
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发表时间：
1988
影响因子：
13.8
通讯作者：
Walsh,KA
中科院分区：
文献类型：
--
作者：
Titani,K;Walsh,KA
血管性血友病因子是一种非常大的、多功能的血浆糖蛋白，在止血中对形成血小板堵塞是必不可少的。最近通过蛋白质和cDNA序列分析进行的结构研究已经建立了整个结构。主干氨基酸序列和多个翻译后加工位点。这一信息和电子显微镜的其他研究为理解这种多聚体蛋白质的多结构域特征提供了结构基础。有限的蛋白水解学研究正在澄清与凝血因子VIII和肝素结合的功能结构域的位置，以及那些连接内皮下大分子和血小板受体的功能结构域。血管性血友病因子(VWF)是一种血浆糖蛋白，它介导血小板与内皮下层的黏附，导致血管损伤部位形成血小板栓。VWF的多功能特性适合于在血小板受体、胶原蛋白、肝素和凝血因子VIII之间发挥多种桥梁功能。vWF功能降低的个体由于血小板凝块的形成障碍而导致出血时间延长。该蛋白在内皮细胞和巨核细胞中合成为300 kDa的前体，并在糖基化、二硫键形成和蛋白水解性切割等处理事件后分泌到血浆中。它以一系列二硫键连接的多聚体形式在血浆中循环，大小从1×103到12×103 kDa，与凝血剂形成络合物。在血管损伤时，vWF复合体与血小板和内皮下细胞外基质的成分相互作用，建立一个屏障网络，暂时减少失血，并作为凝血的焦点。目前，研究人员正在澄清这一网络形成大分子的详细结构，并将其各种结合功能与离散的亚结构域联系起来。
Von Willebrand factor is an unusually large, multifunctional plasma glycoprotein essential for the formation of platelet plugs in hemostasis. Recent structural studies by both protein and cDNA sequence analyses have established the entire. backbone amino acid sequence and many sites of post-translational proce~ ing. This information and other studies by electron microscopy are providing a stnc'tural basis for understanding the multidomain character of this multimeric protein. Limited proteolytic studies are clarifying the location of functional domains that bind factor VIII coagulant and heparin as well as those bridging subendothelial macromolecules to platelet receptors. von Willebrand factor (vWF) is a plasma glycoprotein that mediates platelet adhesion to the subendothelium, leading to the formation of platelet plugs at sites of vascular injury. The multi-functional character of vWF suits it for a variety of bridging functions between platelet receptors, collagen, heparin and coagulation factor VIII. Individuals with reduced levels of vWF function suffer from prolonged bleeding times due to impaired formation of platelet plugs. The protein is synthesized as a 300 kDa precursor in endothelial cells and megakaryocytes, and is secreted into plasma after processing events that include glycosylation, disulfide-bond formation, and proteolytic cleavages. It circulates in plasma as a series of disulfide-linked multimers ranging in mass from 1 x 103 to 12 x 103 kDa, which form complexes with factor VIII coagulant. Upon vascular injury interactions of the vWF complex with platelets and with components of the subendothelial extracellular matrix establish a barrier network that temporarily minimizes blood loss and acts as a focus for blood coagulation. Studies are now clarifying the detailed structure of thi~ networkforming macromolecule and relating its various binding functions to discrete substructural domains.