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-Structure paper
タイトル | Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 3863, Year 2019 |
掲載日 | 2019年8月27日 |
![]() | Suyang Zhang / Thomas Tischer / David Barford / ![]() ![]() |
PubMed 要旨 | The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are ...The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency. |
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手法 | EM (単粒子) |
解像度 | 3.2 - 3.7 Å |
構造データ | ![]() EMDB-4463: ![]() EMDB-4464: EMDB-4465, PDB-6q6g: EMDB-4466, PDB-6q6h: ![]() EMDB-4467: |
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