Local Elongation of Endothelial Cell-anchored von Willebrand Factor Strings Precedes ADAMTS13 Protein-mediated Proteolysis
Local Elongation of Endothelial Cell-anchored von Willebrand Factor Strings Precedes ADAMTS13 Protein-mediated Proteolysis
复制标题
DOI：
10.1074/jbc.m111.271890
复制
发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Vanhoorelbeke, Karen
中科院分区：
文献类型：
--
作者：
De Ceunynck, Karen;Rocha, Susana;Vanhoorelbeke, Karen
锚定在内皮表面的血小板修饰的血管性血友病因子（VWF）链被ADAMTS13快速切割。使用成像和计算软件，探索了ADAMTS13切割位点的单个VWF串特征，如数量、位置和辅助特征。通过以下VWF字符串长度的变化，我们证明了VWF字符串被切割多次，连续缩短字符串长度的函数的时间和产生的片段的大小从5到超过100 μ m。这些比通常在正常血浆中观察到的要大，表明在循环中发生了进一步的蛋白水解。有趣的是，在89%的所有切割事件中，VWF串在ADAMTS13蛋白水解之前在切割位点精确地伸长。这些局部伸长是VWF串的一般特征，与ADAMTS13的存在无关。此外，大的伸长，从1.4到40 μ m的大小范围内，发生在不同地点的空间和时间。总之，ADAMTS13介导的蛋白水解的VWF字符串下流之前的大伸长的字符串在切割位点。这些延伸可能导致许多外切位点同时暴露，从而促进ADAMTS13介导的切割。
Platelet-decorated von Willebrand factor (VWF) strings anchored to the endothelial surface are rapidly cleaved by ADAMTS13. Individual VWF string characteristics such as number, location, and auxiliary features of the ADAMTS13 cleavage sites were explored here using imaging and computing software. By following changes in VWF string length, we demonstrated that VWF strings are cleaved multiple times, successively shortening string length in the function of time and generating fragments ranging in size from 5 to over 100 mu m. These are larger than generally observed in normal plasma, indicating that further proteolysis takes place in circulation. Interestingly, in 89% of all cleavage events, VWF strings elongate precisely at the cleavage site before ADAMTS13 proteolysis. These local elongations are a general characteristic of VWF strings, independent of the presence of ADAMTS13. Furthermore, large elongations, ranging in size from 1.4 to 40 mu m, occur at different sites in space and time. In conclusion, ADAMTS13-mediated proteolysis of VWF strings under flow is preceded by large elongations of the string at the cleavage site. These elongations may lead to the simultaneous exposure of many exosites, thereby facilitating ADAMTS13-mediated cleavage.