Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex
Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex
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DOI：
10.1016/j.cell.2007.01.019
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发表时间：
2007-02-09
期刊：
影响因子：
64.5
通讯作者：
Wu, Hao
中科院分区：
文献类型：
--
作者：
Park, Hyun Ho;Logette, Emmanuelle;Wu, Hao
死亡结构域（DD）超家族的蛋白质介导寡聚信号传导复合物的组装，用于通过未知机制激活半胱天冬酶和激酶。在这里，我们报告的晶体结构的PIDDD DD和RAIDDD DD复合物，它形成的核心的半胱天冬酶-2激活复合物PIDDo体。虽然RAIDDD和PIDDD是单体，但它们组装成包含七个RAIDDD DD和五个PIDDD DD的复合物。尽管使用了非对称组装机制，但复合体中的所有DD都处于准等效环境中。该结构提供了八个独特的非对称接口，可分为三种类型。这三种类型的相互作用一起覆盖了DD表面的大部分。几乎所有界面上的突变导致组装的破坏，导致缺陷的半胱天冬酶-2活化。这三种类型的相互作用可能代表DD超家族中用于组装不同化学计量的复合物的大多数（如果不是全部）相互作用模式。
Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2-activating complex PIDDo-some. Although RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven RAIDD DDs and five PIDD DDs. Despite the use of an asymmetric assembly mechanism, all DDs in the complex are in quasi-equivalent environments. The structure provided eight unique asymmetric interfaces, which can be classified into three types. These three types of interactions together cover a majority of the DD surface. Mutagenesis on almost all interfaces leads to disruption of the assembly, resulting in defective caspase-2 activation. The three types of interactions may represent most, if not all, modes of interactions in the DD superfamily for assembling complexes of different stoichiometry.