Blood：VWF与血小板整合素结合的C4结构域的结构和动力学解析

2018-10-11 MedSci MedSci原创

血管假性血友病因子（VWF）是调控止血的关键因子，可促进招募血小板聚集到血管损伤处。由6个C端结构域形成二聚体C末端VWF阀杆。当剪切力激活时，阀杆变成开放性构象，允许VWF黏附到血小板和血管壁。要解析其潜在分子机制和疾病相关突变所导致的功能紊乱，明确C端结构域的结构和动力学首当其冲。研究人员发现VWF C4结构域的解结构可结合血小板整合素，对VWF功能至关重要。在该结构域中，我们发现了五个子结构

血管假性血友病因子（VWF）是调控止血的关键因子，可促进招募血小板聚集到血管损伤处。由6个C端结构域形成二聚体C末端VWF阀杆。当剪切力激活时，阀杆变成开放性构象，允许VWF黏附到血小板和血管壁。

要解析其潜在分子机制和疾病相关突变所导致的功能紊乱，明确C端结构域的结构和动力学首当其冲。研究人员发现VWF C4结构域的解结构可结合血小板整合素，对VWF功能至关重要。在该结构域中，我们发现了五个子结构域内和域间二硫化亚铁桥，其中一个在C结构域中独一无二。

对结构进一步研究发现了一个不同寻常的铰链双子域排列。铰链被限制在连接两个子域的V2547附件的一个非常短的片段内。该铰链与相邻的两个子域间二硫化亚铁桥一起，诱导两个子域相对彼此发生缓慢的构象变化和位置变动。除此之外，研究人员进一步证实了一个临床上的功能获得性VWF突变（Y2561）更可能影响C4结构域与邻近结构域的排列，而不是影响血小板整合素结合。

原始出处：

Emma-Ruoqi Xu，et. Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor. Blood 2018 ：blood-2018-04-843615； doi： https：//doi.org/10.1182/blood-2018-04-843615

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2019-05-11 gjsgj

#结构域#

50 0
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2019-07-24 hongbochen

#解析#

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2018-10-13 sunmin0219

#vWF#

45 0
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2018-10-13 智智灵药

#整合素#

37 0
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2018-10-11 xuexin53

学习

79 0
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2018-10-11 天地飞扬

了解一下，谢谢分享！

62 0
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2018-10-11 1e145228m78(暂无匿称)

学习了，谢谢作者分享!

80 0
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2018-10-11 医者仁心5538

学习了

71 0

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