Sequence and structure relationships within von Willebrand factorSequence and structure relationships within von Willebrand factor
Sequence and structure relationships within von Willebrand factorSequence and structure relationships within von Willebrand factor
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DOI：
10.1182/blood-2012-01-405134
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发表时间：
2012-07-12
期刊：
影响因子：
20.3
通讯作者：
Springer, Timothy A.
中科院分区：
文献类型：
--
作者：
Zhou, Yan-Feng;Eng, Edward T.;Springer, Timothy A.
在本研究中，我们重新注释了von Willebrand因子（VWF），将其整个序列分配给特定的模块，并使用电子显微镜（EM）将这些模块与结构相关联。D域是EM中可见的更小模块的集合。D-结构域组件中的模块包括von Willebrand D，8-半胱氨酸，胰蛋白酶通道样，E或纤连蛋白1型样结构域，以及D4中独特的D4 N模块。D1-D2前结构域显示2个大的连接组件，每个组件包含较小的叶。VWF的前B和C区被重新注释为6个串联的von Willebrand C（VWC）和VWC样结构域。这6个VWC结构域对应于在VWF二聚体束的茎区中在酸性pH下成对缔合的6个延长结构域。整合素α（IIb）β（3）与EM中可见的第四个模块VWC 4（其带有VWF Arg-Gly-Asp基序）的结合证明了这种对应关系。C-末端胱氨酸结结构域以通过与TGF-β的同源性预测的方式端对端二聚化，并且在二聚体簇中取向大致垂直于VWC结构域。VWF中的结构域与其他蛋白质中的结构域的同源性允许许多二硫键被暂时分配，这可能具有功能上的影响。（血。2012;120（2）：449-458）
In the present study, we re-annotated von Willebrand factor (VWF), assigned its entire sequence to specific modules, and related these modules to structure using electron microscopy (EM). The D domains are assemblies of smaller modules visible as lobes in EM. Modules in the D-domain assemblies include von Willebrand D, 8-cysteine, trypsin inhibitor-like, E or fibronectin type 1-like domains, and a unique D4N module in D4. The D1-D2 prodomain shows 2 large connected assemblies, each containing smaller lobes. The previous B and C regions of VWF are re-annotated as 6 tandem von Willebrand C (VWC) and VWC-like domains. These 6 VWC domains correspond to 6 elongated domains that associate in pairs at acidic pH in the stem region of VWF dimeric bouquets. This correspondence is demonstrated by binding of integrin alpha(IIb)beta(3) to the fourth module seen in EM, VWC4, which bears the VWF Arg-Gly-Asp motif. The C-terminal cystine knot domain dimerizes end-to-end in a manner predicted by homology to TGF-beta and orients approximately perpendicular to the VWC domains in dimeric bouquets. Homologies of domains in VWF to domains in other proteins allow many disulfide bonds to be tentatively assigned, which may have functional implications. (Blood. 2012;120(2):449-458)