Structural Analysis of the Anaphase-Promoting Complex Reveals Multiple Active Sites and Insights into Polyubiquitylation

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase composed of ∼13 distinct subunits required for progression through meiosis, mitosis, and the G1 phase of the cell cycle. Despite its central role in these processes, information concerning its composition and structure is lim...

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Veröffentlicht in:Molecular cell 2005-12, Vol.20 (6), p.855-866
Hauptverfasser: Passmore, Lori A., Booth, Christopher R., Vénien-Bryan, Catherine, Ludtke, Steven J., Fioretto, Céline, Johnson, Louise N., Chiu, Wah, Barford, David
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Sprache:eng
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Zusammenfassung:The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase composed of ∼13 distinct subunits required for progression through meiosis, mitosis, and the G1 phase of the cell cycle. Despite its central role in these processes, information concerning its composition and structure is limited. Here, we determined the structure of yeast APC/C by cryo-electron microscopy (cryo-EM). Docking of tetratricopeptide repeat (TPR)-containing subunits indicates that they likely form a scaffold-like outer shell, mediating assembly of the complex and providing potential binding sites for regulators and substrates. Quantitative determination of subunit stoichiometry indicates multiple copies of specific subunits, consistent with a total APC/C mass of ∼1.7 MDa. Moreover, yeast APC/C forms both monomeric and dimeric species. Dimeric APC/C is a more active E3 ligase than the monomer, with greatly enhanced processivity. Our data suggest that multimerisation and/or the presence of multiple active sites facilitates the APC/C's ability to elongate polyubiquitin chains.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2005.11.003