4aez

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Crystal Structure of Mitotic Checkpoint ComplexCrystal Structure of Mitotic Checkpoint Complex

Structural highlights

4aez is a 9 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SLP1_SCHPO Required for mad2-dependent spindle checkpoint activation. Promotes ubiquitin-dependent degradation of cdc13 by the anaphase promoting complex/cyclosome (APC/C).[1] [2] [3]

Publication Abstract from PubMed

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.

Structure of the mitotic checkpoint complex.,Chao WC, Kulkarni K, Zhang Z, Kong EH, Barford D Nature. 2012 Mar 21;484(7393):208-13. doi: 10.1038/nature10896. PMID:22437499[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Izawa D, Goto M, Yamashita A, Yamano H, Yamamoto M. Fission yeast Mes1p ensures the onset of meiosis II by blocking degradation of cyclin Cdc13p. Nature. 2005 Mar 24;434(7032):529-33. PMID:15791259 doi:http://dx.doi.org/10.1038/nature03406
  2. ↑ Matsumoto T. A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2. Mol Cell Biol. 1997 Feb;17(2):742-50. PMID:9001228
  3. ↑ Kim SH, Lin DP, Matsumoto S, Kitazono A, Matsumoto T. Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science. 1998 Feb 13;279(5353):1045-7. PMID:9461438
  4. ↑ Chao WC, Kulkarni K, Zhang Z, Kong EH, Barford D. Structure of the mitotic checkpoint complex. Nature. 2012 Mar 21;484(7393):208-13. doi: 10.1038/nature10896. PMID:22437499 doi:10.1038/nature10896

4aez, resolution 2.30Å

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