6Q6H

Cryo-EM structure of the APC/C-Cdc20-Cdk2-cyclinA2-Cks2 complex, the D2 box class

Summary for 6Q6H

• Entry DOI: 10.2210/pdb6q6h/pdb
• EMDB information: 4463 4464 4465 4466 4467
• Descriptor: Anaphase-promoting complex subunit 10, Anaphase-promoting complex subunit 13, Anaphase-promoting complex subunit 16, ... (16 entities in total)
• Functional Keywords: spindle assembly checkpoint, anaphase-promoting complex, cyclin, ubiquitination, cell cycle
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 21
• Total formula weight: 1262162.38

Authors

Zhang, S.,Barford, D. (deposition date: 2018-12-11, release date: 2019-09-11, Last modification date: 2024-05-15)

Primary citation

Zhang, S.,Tischer, T.,Barford, D.
Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C.
Nat Commun, 10:3863-3863, 2019

PubMed Abstract: 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.

PubMed: 31455778
DOI: 10.1038/s41467-019-11833-2

Experimental method

ELECTRON MICROSCOPY (3.2 Å)