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TitleAtomic structure of the APC/C and its mechanism of protein ubiquitination.
Journal, issue, pagesNature, Vol. 522, Issue 7557, Page 450-454, Year 2015
Publish dateJun 25, 2015
AuthorsLeifu Chang / Ziguo Zhang / Jing Yang / Stephen H McLaughlin / David Barford /
PubMed AbstractThe 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 ...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.
External linksNature / PubMed:26083744 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 7.3 Å
Structure data

2924

4ui9

EMDB-2924: Cryo-EM structure of the human APC/C-Cdh1-Emi1 ternary complex at 3.6 angstrom resolution.
PDB-4ui9: Atomic structure of the human Anaphase-Promoting Complex
Method: EM (single particle) / Resolution: 3.6 Å

2925

5a31

EMDB-2925: Cryo-EM structure of the human APC/C-Cdh1-Hsl1-UbcH10-Ub complex.
PDB-5a31: Structure of the human APC-Cdh1-Hsl1-UbcH10 complex.
Method: EM (single particle) / Resolution: 5.7 Å

EMDB-2926:
Cryo-EM structure of the human APC/C-Cdh1-Hsl1-UbcH10 complex.
Method: EM (single particle) / Resolution: 7.3 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsCELL CYCLE / UBIQUITINATION / APC/C / APC SUBUNITS / ANAPHASE PROMOTING COMPLEX

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