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-Structure paper
タイトル | Molecular mechanisms of APC/C release from spindle assembly checkpoint inhibition by APC/C SUMOylation. |
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ジャーナル・号・ページ | Cell Rep, Vol. 34, Issue 13, Page 108929, Year 2021 |
掲載日 | 2021年3月30日 |
著者 | Stanislau Yatskevich / Jessie S Kroonen / Claudio Alfieri / Thomas Tischer / Anna C Howes / Linda Clijsters / Jing Yang / Ziguo Zhang / Kaige Yan / Alfred C O Vertegaal / David Barford / |
PubMed 要旨 | The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the ...The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) is coordinated with the attachment of sister chromatids to the mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand the structural and functional consequences of APC/C SUMOylation, we reconstituted SUMOylated APC/C for electron cryo-microscopy and biochemical analyses. SUMOylation of the APC/C causes a substantial rearrangement of the WHB domain of APC/C's cullin subunit (APC2). Although APC/C SUMOylation results in a modest impact on normal APC/C activity, repositioning APC2 reduces the affinity of APC/C for the mitotic checkpoint complex (MCC), the effector of the SAC. This attenuates MCC-mediated suppression of APC/C activity, allowing for more efficient ubiquitination of APC/C substrates in the presence of the MCC. Thus, SUMOylation stimulates the reactivation of APC/C when the SAC is silenced, contributing to timely anaphase onset. |
リンク | Cell Rep / PubMed:33789095 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.78 - 3.99 Å |
構造データ | EMDB-10536, PDB-6tnt: EMDB-10538: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | CELL CYCLE / APC/C / APC2 / WHB domain / SUMOylation |