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Structural basis for the subunit assembly of the anaphase-promoting complex

机译:后期促进复合物亚基组装的结构基础

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摘要

The anaphase-promoting complex or cyclosome (APC/C) is an unusually large E3 ubiquitin ligase responsible for regulating defined cell cycle transitions. Information on how its 13 constituent proteins are assembled, and how they interact with co-activators, substrates and regulatory proteins is limited. Here, we describe a recombinant expression system that allows the reconstitution of holo APC/C and its sub-complexes that, when combined with electron microscopy, mass spectrometry and docking of crystallographic and homology-derived coordinates, provides a precise definition of the organization and structure of all essential APC/C subunits, resulting in a pseudo-atomic model for 70% of the APC/C. A lattice-like appearance of the APC/C is generated by multiple repeat motifs of most APC/C subunits. Three conserved tetratricopeptide repeat (TPR) subunits (Cdcl6, Cdc23 and Cdc27) share related superhelical homo-dimeric architectures that assemble to generate a quasi-symmetrical structure. Our structure explains how this TPR sub-complex, together with additional scaffolding subunits (Apcl, Apc4 and Apc5), coordinate the juxtaposition of the catalytic and substrate recognition module (Apc2, Apcll and ApclO (also known as Docl)), and TPR-phosphorylation sites, relative to co-activator, regulatory proteins and substrates.
机译:后期促进复合物或环体(APC / C)是一种异常大的E3泛素连接酶,负责调节确定的细胞周期转换。关于其13种组成蛋白如何组装以及它们如何与共激活因子,底物和调节蛋白相互作用的信息有限。在这里,我们描述了一种重组表达系统,该系统可以重建完整的APC / C及其亚复合物,当与电子显微镜,质谱法以及晶体学和同源性坐标对接相结合时,可提供该组织的精确定义和所有必不可少的APC / C亚基的结构,从而为70%的APC / C建立了伪原子模型。 APC / C的格子状外观是由大多数APC / C亚基的多个重复基序产生的。三个保守的四肽重复(TPR)亚基(Cdcl6,Cdc23和Cdc27)共享相关的超螺旋同二聚体结构,这些结构可组装以生成准对称结构。我们的结构说明了该TPR子复合物与其他支架亚基(Apcl,Apc4和Apc5)如何协调催化和底物识别模块(Apc2,Apcll和ApclO(也称为Docl))和TPR-相对于共激活因子,调节蛋白和底物的磷酸化位点。

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  • 来源
    《Nature》 |2011年第7333期|p.227-232|共6页
  • 作者单位

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Department of Chemistry, University of Oxford, South Parks Road,Oxford, 0X1 3TA, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Department of Chemistry, University of Oxford, South Parks Road,Oxford, 0X1 3TA, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

    Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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