Crystal Structure of the Caenorhabditis elegans Apoptosome Reveals an Octameric Assembly of CED-4
Crystal Structure of the Caenorhabditis elegans Apoptosome Reveals an Octameric Assembly of CED-4
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DOI：
10.1016/j.cell.2010.03.017
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发表时间：
2010-04-30
期刊：
影响因子：
64.5
通讯作者：
Shi, Yigong
中科院分区：
文献类型：
--
作者：
Qi, Shiqian;Pang, Yuxuan;Shi, Yigong
CED-4同源寡聚体或溶酶体通过促进CED-3半胱天冬酶酶原的自催化活化而为秀丽隐杆线虫中程序性细胞死亡的起始所需。CED-4核糖体如何组装和激活CED-3仍然是个谜。在这里，我们报告了完整的CED-4溶酶体的晶体结构，并表明它由8个CED-4分子组成，通过AAA（+）ATP酶之间以前未报道的界面组织为不对称二聚体的四聚体。这八个CED-4分子形成漏斗状结构。成熟的CED-3蛋白酶在溶液中是单体，并与CED-4溶酶体形成活性全酶，在该溶酶体中CED-3的蛋白酶活性被显著地刺激。出乎意料的是，八聚体CED-4核糖体似乎仅结合成熟CED-3的两个而不是八个分子。CED-4溶酶体的结构揭示了AAA（+）ATP酶的NB-ARC家族的共同原理，并提出了CED-3激活的机制。
The CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death in Caenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How the CED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystal structure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organized as a tetramer of an asymmetric dimer via a previously unreported interface among AAA(+) ATPases. These eight CED-4 molecules form a funnel-shaped structure. The mature CED-3 protease is monomeric in solution and forms an active holoenzyme with the CED-4 apoptosome, within which the protease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosome appears to bind only two, not eight, molecules of mature CED-3. The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3.