5LCW

Cryo-EM structure of the Anaphase-promoting complex/Cyclosome, in complex with the Mitotic checkpoint complex (APC/C-MCC) at 4.2 angstrom resolution

Summary for 5LCW

• Entry DOI: 10.2210/pdb5lcw/pdb
• EMDB information: 4037
• Descriptor: Anaphase-promoting complex subunit 1, Anaphase-promoting complex subunit 10, Anaphase-promoting complex subunit 13, ... (18 entities in total)
• Functional Keywords: complex, ubiquitin, e3 ligase, ubiquitin ligase, cullin, ring, cell cycle, mitosis, spindle checkpoint, degron
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 23
• Total formula weight: 1331085.90

Authors

Alfieri, C.,Chang, L.,Zhang, Z.,Yang, J.,Maslen, S.,Skehel, M.,Barford, D. (deposition date: 2016-06-22, release date: 2016-08-10, Last modification date: 2024-10-09)

Primary citation

Alfieri, C.,Chang, L.,Zhang, Z.,Yang, J.,Maslen, S.,Skehel, M.,Barford, D.
Molecular basis of APC/C regulation by the spindle assembly checkpoint.
Nature, 536:431-436, 2016

PubMed Abstract: In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores to the mitotic spindle with activation of the anaphase-promoting complex (APC/C), the E3 ubiquitin ligase responsible for initiating chromosome separation. In response to unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC), which inhibits the APC/C and delays chromosome segregation. By cryo-electron microscopy, here we determine the near-atomic resolution structure of a human APC/C–MCC complex (APC/C(MCC)). Degron-like sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator subunit responsible for substrate interactions. BubR1 also obstructs binding of the initiating E2 enzyme UbcH10 to repress APC/C ubiquitination activity. Conformational variability of the complex enables UbcH10 association, and structural analysis shows how the Cdc20 subunit intrinsic to the MCC (Cdc20(MCC)) is ubiquitinated, a process that results in APC/C reactivation when the SAC is silenced.

PubMed: 27509861
DOI: 10.1038/nature19083

Experimental method

ELECTRON MICROSCOPY (4.2 Å)