Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation
Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation
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DOI：
10.1126/science.1195821
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发表时间：
2010-12-23
期刊：
影响因子：
56.9
通讯作者：
Gros, Piet
中科院分区：
文献类型：
--
作者：
Forneris, Federico;Ricklin, Daniel;Gros, Piet
补体级联的激活诱导炎症反应并标记用于免疫清除的细胞。在中心补体扩增步骤中，由表面结合的C3 B和因子B组成的复合物被因子D切割，以在靶向表面上产生活性转化酶。我们目前的晶体结构的前转化酶C3bB在4埃的分辨率和其复杂的D因子在3.5埃的分辨率。我们的数据显示了因子B如何与C3 B结合形成C3 b B的开放“活化”状态。因子D通过远离催化中心的位点特异性结合因子B的开放构象，并被底物激活，其置换因子D的自抑制环。这种协同的蛋白水解机制，这是辅因子依赖性和底物诱导，限制补体扩增C3b标记的靶细胞。
Activation of the complement cascade induces inflammatory responses and marks cells for immune clearance. In the central complement-amplification step, a complex consisting of surface-bound C3b and factor B is cleaved by factor D to generate active convertases on targeted surfaces. We present crystal structures of the pro-convertase C3bB at 4 angstrom resolution and its complex with factor D at 3.5 angstrom resolution. Our data show how factor B binding to C3b forms an open "activation" state of C3bB. Factor D specifically binds the open conformation of factor B through a site distant from the catalytic center and is activated by the substrate, which displaces factor D's self-inhibitory loop. This concerted proteolytic mechanism, which is cofactor-dependent and substrate-induced, restricts complement amplification to C3b-tagged target cells.