Monomeric structures of the zymogen and active catalytic domain of complement protease C1r: Further insights into the C1 activation mechanism
Monomeric structures of the zymogen and active catalytic domain of complement protease C1r: Further insights into the C1 activation mechanism
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DOI：
10.1016/s0969-2126(02)00881-x
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发表时间：
2002-11-01
期刊：
影响因子：
5.7
通讯作者：
Gaboriaud, C
中科院分区：
文献类型：
--
作者：
Budayova-Spano, M;Grabarse, W;Gaboriaud, C
C1 r是丝氨酸蛋白酶（SP），介导C1的自激活，C1是触发经典补体途径的复合物。我们已经确定了两个片段的晶体结构，从人类C1 R催化结构域，每个包含第二补体控制蛋白（CCP 2）模块和SP域。野生型物种具有活性结构，而S637 A突变体是酶原。该结构揭示了CCP 2-SP界面的受限铰链柔性，并且两者都以环E的独特α-螺旋构象为特征。酶原激活结构域具有高的流动性，和活性结构显示出有限的访问大多数底物结合亚位点。与C1 r自激活过程相关的进一步影响来自晶体中的蛋白质-蛋白质相互作用。
C1r is the serine protease (SP) that mediates autoactivation of C1, the complex that triggers the classical complement pathway. We have determined the crystal structure of two fragments from the human C1r catalytic domain, each encompassing the second complement control protein (CCP2) module and the SP domain. The wild-type species has an active structure, whereas the S637A mutant is a zymogen. The structures reveal a restricted hinge flexibility of the CCP2-SP interface, and both are characterized by the unique alpha-helical conformation of loop E. The zymogen activation domain exhibits high mobility, and the active structure shows a restricted access to most substrate binding subsites. Further implications relevant to the C1r self-activation process are derived from protein-protein interactions in the crystals.