RAIDD is a new 'death' adaptor molecule
RAIDD is a new 'death' adaptor molecule
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DOI：
10.1038/385086a0
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发表时间：
1997-01-02
期刊：
影响因子：
64.8
通讯作者：
Dixit, VM
中科院分区：
文献类型：
--
作者：
Duan, H;Dixit, VM
细胞死亡途径的效应臂由属于ICE/CED-3家族的半胱氨酸蛋白酶组成（1，2）。在后生动物细胞中，它们作为无活性的多肽前体（酶原）存在，每个前体由一个前结构域和一个大小不等的催化亚基组成，前结构域被切割以激活蛋白酶。这些“死亡”蛋白酶与信号通路的偶联可能是由含有蛋白质-蛋白质相互作用基序的衔接分子介导的，例如死亡结构域（1）。我们描述了这样一种接头分子，RAIDD，它具有不寻常的二分结构，包括一个羧基末端死亡结构域，该结构域与RIP中的同源结构域结合，RIP是死亡途径的丝氨酸/苏氨酸激酶组分（3，4）。氨基末端结构域与两个ICE/CED-3家族成员的前结构域序列惊人地同源，所述ICE/CED-3家族成员是人ICH-1（参考文献5）和秀丽隐杆线虫CED-3（参考文献6）。该类似区域介导RAIDD与ICH-1和CED-3的结合，作为与死亡蛋白酶的直接连接，表明前结构域可以通过嗜同性相互作用决定ICE/CED-3酶原与调节衔接子分子结合的特异性。最后，N端结构域序列的改变相当于C端失活突变。秀丽线虫ced-3基因（7，8）阻止嗜同性结合，突出了这种相互作用的潜在原始性质。
THE effector arm of the the cell-death pathway is composed of cysteine proteases belonging to the ICE/CED-3 family(1,2). In metazoan cells these exist as inactive polypeptide precursors (zymogens), each composed of a prodomain, which is cleaved to activate the protease, and a large and small catalytic subunit. The coupling of these 'death' proteases to signalling pathways is probably mediated by adaptor molecules that contain protein-protein interaction motifs such as the death domain(1). Were we describe such an adaptor molecule, RAIDD, which has an unusual bipartite architecture comprising a carboxy-terminal death domain that binds to the homologous domain in RIP, a serine/threonine kinase component of the death pathway(3,4). The amino-terminal domain is surprisingly homologous with the sequence of the prodomain of two ICE/CED-3 family members, human ICH-1 (ref. 5) and Caenorhabditis elegans CED-3 (ref. 6). This similar region mediates the binding of RAIDD to ICH-1 and CED-3, serving as a direct link to the death proteases, indicating that the prodomain may, through homophilic interactions, determine the specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules. Finally, alternations in the sequence of the N-terminal domain that are equivalent to inactivating mutations in the C. elegans ced-3 gene(7,8) prevent homophilic binding, highlighting the potentially primordial nature of this interaction.