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

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.
Mesh Terms:
Anaphase-Promoting Complex-Cyclosome, Apc1 Subunit, Anaphase-Promoting Complex-Cyclosome, Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome, Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome, Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome, Apc8 Subunit, Anaphase-Promoting Complex-Cyclosome, Cadherins, Catalytic Domain, Cell Cycle Proteins, Cryoelectron Microscopy, Cytoskeletal Proteins, F-Box Proteins, Humans, Lysine, Models, Molecular, Phosphorylation, Protein Binding, Protein Subunits, Structure-Activity Relationship, Substrate Specificity, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination
Nature
Date: Jun. 25, 2015
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