4AEZ

Crystal Structure of Mitotic Checkpoint Complex

Summary for 4AEZ

• Entry DOI: 10.2210/pdb4aez/pdb
• Descriptor: WD REPEAT-CONTAINING PROTEIN SLP1, MITOTIC SPINDLE CHECKPOINT COMPONENT MAD2, MITOTIC SPINDLE CHECKPOINT COMPONENT MAD3, ... (4 entities in total)
• Functional Keywords: cell cycle, ken-box, d-box, apc/c
• Biological source: SCHIZOSACCHAROMYCES POMBE (FISSION YEAST); More
• Total number of polymer chains: 9
• Total formula weight: 281523.90

Authors

Kulkarni, K.A.,Chao, W.C.H.,Zhang, Z.,Barford, D. (deposition date: 2012-01-13, release date: 2012-03-21, Last modification date: 2023-12-20)

Primary citation

Chao, W.C.H.,Kulkarni, K.A.,Zhang, Z.,Kong, E.H.,Barford, D.
Structure of the Mitotic Checkpoint Complex
Nature, 484:208-, 2012

PubMed Abstract: In mitosis, the spindle assembly checkpoint (SAC) ensures genome stability by delaying chromosome segregation until all sister chromatids have achieved bipolar attachment to the mitotic spindle. The SAC is imposed by the mitotic checkpoint complex (MCC), whose assembly is catalysed by unattached chromosomes and which binds and inhibits the anaphase-promoting complex/cyclosome (APC/C), the E3 ubiquitin ligase that initiates chromosome segregation. Here, using the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20), we reveal the molecular basis of MCC-mediated APC/C inhibition and the regulation of MCC assembly. The MCC inhibits the APC/C by obstructing degron recognition sites on Cdc20 (the substrate recruitment subunit of the APC/C) and displacing Cdc20 to disrupt formation of a bipartite D-box receptor with the APC/C subunit Apc10. Mad2, in the closed conformation (C-Mad2), stabilizes the complex by optimally positioning the Mad3 KEN-box degron to bind Cdc20. Mad3 and p31(comet) (also known as MAD2L1-binding protein) compete for the same C-Mad2 interface, which explains how p31(comet) disrupts MCC assembly to antagonize the SAC. This study shows how APC/C inhibition is coupled to degron recognition by co-activators.

PubMed: 22437499
DOI: 10.1038/NATURE10896

Experimental method

X-RAY DIFFRACTION (2.3 Å)