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Atomic structure of the APC/C and its mechanism of protein ubiquitination

Author

Listed:
  • Leifu Chang

    (MRC Laboratory of Molecular Biology)

  • Ziguo Zhang

    (MRC Laboratory of Molecular Biology)

  • Jing Yang

    (MRC Laboratory of Molecular Biology)

  • Stephen H. McLaughlin

    (MRC Laboratory of Molecular Biology)

  • David Barford

    (MRC Laboratory of Molecular Biology)

Abstract

The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex and interphase early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use cryo-electron microscopy to determine atomic structures of APC/C–coactivator complexes with either Emi1 or a UbcH10–ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10–ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of future experiments to investigate APC/C functions in vivo.

Suggested Citation

  • Leifu Chang & Ziguo Zhang & Jing Yang & Stephen H. McLaughlin & David Barford, 2015. "Atomic structure of the APC/C and its mechanism of protein ubiquitination," Nature, Nature, vol. 522(7557), pages 450-454, June.
    • Handle: RePEc:nat:nature:v:522:y:2015:i:7557:d:10.1038_nature14471
    DOI: 10.1038/nature14471
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    Cited by:

    1. Sang Bae Lee & Luciano Garofano & Aram Ko & Fulvio D’Angelo & Brulinda Frangaj & Danika Sommer & Qiwen Gan & KyeongJin Kim & Timothy Cardozo & Antonio Iavarone & Anna Lasorella, 2022. "Regulated interaction of ID2 with the anaphase-promoting complex links progression through mitosis with reactivation of cell-type-specific transcription," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Shizhong Ke & Fabin Dang & Lin Wang & Jia-Yun Chen & Mandar T. Naik & Wenxue Li & Abhishek Thavamani & Nami Kim & Nandita M. Naik & Huaxiu Sui & Wei Tang & Chenxi Qiu & Kazuhiro Koikawa & Felipe Batal, 2024. "Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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