Deciphering the fine details of c1 assembly and activation mechanisms: "mission impossible"?

Deciphering the fine details of c1 assembly and activation mechanisms: "mission impossible"?
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DOI:
10.3389/fimmu.2014.00565
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发表时间:
2014
影响因子:
7.3
通讯作者:
Rossi V
Rossi V
中科院分区:
医学2区
文献类型:
--
作者:
Gaboriaud C;Ling WL;Thielens NM;Bally I;Rossi V

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经典的补体途径是由大的(~800 kDa)和灵活的多聚体C1复合体启动的。它的催化功能是由与C1q传感单元相关的蛋白酶异四聚体C1r2s2触发的,C1q传感单元是一个由18条链组成的复杂组装,作为杂三聚体的六角体。最初的开创性研究深入了解了C1建筑群的主要建筑原则。然后,解剖策略提供了其主要功能和/或结构构建块的高分辨率结构,以及一些关键蛋白质-蛋白质相互作用的结构细节。这些过去和现在的发现将被简要总结,以解决什么仍然定义不清的问题。从功能的角度出发,我们将描述决定C1活性及其严密调控的主要分子决定因素。目前的观点仍然是破译C1在体内的真正工作方式和控制方式,无论是在正常情况下还是在病理情况下。
The classical complement pathway is initiated by the large (~800 kDa) and flexible multimeric C1 complex. Its catalytic function is triggered by the proteases hetero-tetramer C1r2s2, which is associated to the C1q sensing unit, a complex assembly of 18 chains built as a hexamer of heterotrimers. Initial pioneering studies gained insights into the main architectural principles of the C1 complex. A dissection strategy then provided the high-resolution structures of its main functional and/or structural building blocks, as well as structural details on some key protein–protein interactions. These past and current discoveries will be briefly summed up in order to address the question of what is still ill-defined. On a functional point of view, the main molecular determinants of C1 activation and its tight control will be delineated. The current perspective remains to decipher how C1 really works and is controlled in vivo, both in normal and pathological settings.
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