Molecular architecture and mechanism of the anaphase-promoting complex.
Molecular architecture and mechanism of the anaphase-promoting complex.
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DOI：
10.1038/nature13543
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发表时间：
2014-09-18
期刊：
影响因子：
64.8
通讯作者：
Barford, David
中科院分区：
文献类型：
--
作者：
Chang, Leifu;Zhang, Ziguo;Yang, Jing;McLaughlin, Stephen H.;Barford, David
细胞周期调节蛋白的泛素化由后期促进复合体/环体(APC/C)控制姐妹染色单体的分离、胞质分裂和G1期的建立。APC/C是一种非常大的多聚体剔除环连合酶。它的活性严格依赖于促进APC/C-底物相互作用并刺激其催化反应的调节共激活亚基。由于许多APC/C亚单位的结构及其在组装中的组织尚不清楚，因此这些过程的分子基础尚不清楚。在这里，通过对一个人的APC/C-共激活剂-底物复合体的冷冻-EM重建，我们已经确定了该复合体的完整的二级结构。有了这些信息，我们确定了结构上未鉴定的亚基的蛋白质折叠，以及1.2MDA组装中所有20个APC/C亚基的确切位置。与apo APC/C的比较表明，共激活剂促进了深刻的变构转变，涉及到相对于辅助激活剂和Apc10的降解识别模块的剔除环催化亚基的置换。伴随这一转变的是剔除环亚单位的灵活性增加和对UbcH10~泛素亲和力的增强，这可能有助于辅活化子介导的APC/C E3连接酶活性的刺激。
The ubiquitination of cell cycle regulatory proteins by the anaphase-promoting complex/cyclosome (APC/C) controls sister chromatid segregation, cytokinesis and the establishment of G1. The APC/C is an unusually large multimeric cullin-RING ligase. Its activity is strictly dependent on regulatory coactivator subunits that promote APC/C – substrate interactions and stimulate its catalytic reaction. Because the structures of many APC/C subunits and their organization within the assembly are unknown, the molecular basis for these processes is poorly understood. Here, from a cryo-EM reconstruction of a human APC/C-coactivator-substrate complex at 7.4 Å resolution, we have determined the complete secondary structural architecture of the complex. With this information we identified protein folds for structurally uncharacterized subunits, and the definitive location of all 20 APC/C subunits within the 1.2 MDa assembly. Comparison with apo APC/C shows that coactivator promotes a profound allosteric transition involving displacement of the cullin-RING catalytic subunits relative to the degron recognition module of coactivator and Apc10. This transition is accompanied by increased flexibility of the cullin-RING subunits and enhanced affinity for UbcH10~ubiquitin, changes which may contribute to coactivator-mediated stimulation of APC/C E3 ligase activity.
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影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
影响因子：
16
作者：
Das, Ranabir;Mariano, Jennifer;Tsai, Yien Che;Kalathur, Ravi C.;Kostova, Zlatka;Li, Jess;Tarasov, Sergey G.;McFeeters, Robert L.;Altieri, Amanda S.;Ji, Xinhua;Byrd, R. Andrew;Weissman, Allan M.
通讯作者：
Weissman, Allan M.
影响因子：
21.3
作者：
Izawa D;Pines J
通讯作者：
Pines J
影响因子：
9.2
作者：
Carroll, CW;Enquist-Newman, M;Morgan, DO
通讯作者：
Morgan, DO
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K