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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Roles of the anaphase-promoting complex cyclosome and of its activator Cdc20 in functional substrate binding
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Roles of the anaphase-promoting complex cyclosome and of its activator Cdc20 in functional substrate binding

机译：促进后期复杂环体及其激活剂Cdc20在功能性底物结合中的作用

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摘要

The anaphase-promoting complex cyclosome (APC/C) is a multi-subunit ubiquitin-protein ligase that targets for degradation cell-cycle regulatory proteins during exit from mitosis and in the G_1 phase of the cell cycle. The activity of APC/C in mitosis and in G_1 requires interaction with the activator proteins Cdc20 and Cdh1, respectively. Substrates of APC, C-Cdc20 contain a recognition motif called the "destruction box" (D-box). The mode of the action of APC/C activators and their possible role in substrate binding remain poorly understood. Several investigators suggested that Cdc20 and Cdh1 mediate substrate recognition, whereas others proposed that substrates bind to APC/C or to APC/C-activator complexes. All these studies used binding assays, which do not necessarily indicate that substrate binding is functional and leads to product formation. In the present investigation we examined this problem by an "isotope-trapping" approach that directly demonstrates productive substrate binding. With this method we found that the simultaneous presence of both APC/C and Cdc20 is required for functional substrate binding. By contrast, with conventional binding assays we found that either Cdc20 or APC/C can bind substrate by itself, but only at low affinity and relaxed selectivity for D-box. Our results are consistent with models in which interaction of substrate with specific binding sites on both APC/C and Cdc20 is involved in selective and productive substrate binding.
机译：后期促进复合物环体（APC / C）是一种多亚基泛素蛋白连接酶，可在有丝分裂退出和细胞周期G_1期靶向降解细胞周期调节蛋白。 APC / C在有丝分裂和G_1中的活性分别需要与激活蛋白Cdc20和Cdh1相互作用。 APC的基材C-Cdc20包含一个称为“破坏盒”（D-box）的识别图案。 APC / C激活剂的作用方式及其在底物结合中的可能作用仍知之甚少。一些研究者建议Cdc20和Cdh1介导底物识别，而其他研究者则建议底物与APC / C或APC / C激活物复合物结合。所有这些研究都使用了结合试验，这不一定表明底物结合是有功能的并导致产物形成。在本研究中，我们通过直接证明生产性底物结合的“同位素捕获”方法研究了这个问题。通过这种方法，我们发现功能性底物结合需要同时存在APC / C和Cdc20。相比之下，通过常规结合测定，我们发现Cdc20或APC / C都可以自身结合底物，但仅对D-box具有低亲和力和宽松的选择性。我们的结果与模型相一致，在该模型中，底物与APC / C和Cdc20上特定结合位点的相互作用涉及选择性和生产性底物结合。

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