Show simple item record

dc.contributor.authorAlfieri, C
dc.contributor.authorChang, L
dc.contributor.authorZhang, Z
dc.contributor.authorYang, J
dc.contributor.authorMaslen, S
dc.contributor.authorSkehel, M
dc.contributor.authorBarford, D
dc.date.accessioned2020-07-08T09:37:34Z
dc.date.issued2016-08-10
dc.identifier.citationNature, 2016, 536 (7617), pp. 431 - 436
dc.identifier.issn0028-0836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3820
dc.identifier.eissn1476-4687
dc.identifier.doi10.1038/nature19083
dc.description.abstractIn 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.
dc.formatPrint-Electronic
dc.format.extent431 - 436
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectKinetochores
dc.subjectHumans
dc.subjectUbiquitin-Conjugating Enzymes
dc.subjectUbiquitin-Protein Ligases
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectCell Cycle Proteins
dc.subjectProtein Subunits
dc.subjectCryoelectron Microscopy
dc.subjectChromosome Segregation
dc.subjectProtein Conformation
dc.subjectProtein Binding
dc.subjectStructure-Activity Relationship
dc.subjectModels, Molecular
dc.subjectUbiquitination
dc.subjectBiocatalysis
dc.subjectM Phase Cell Cycle Checkpoints
dc.subjectSpindle Apparatus
dc.subjectAnaphase-Promoting Complex-Cyclosome
dc.subjectCdc20 Proteins
dc.titleMolecular basis of APC/C regulation by the spindle assembly checkpoint.
dc.typeJournal Article
dcterms.dateAccepted2016-07-06
rioxxterms.versionofrecord10.1038/nature19083
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2016-08-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature
pubs.issue7617
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Molecular mechanisms of cell cycle regulation
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Molecular mechanisms of cell cycle regulation
pubs.publication-statusPublished
pubs.volume536
pubs.embargo.termsNo embargo
icr.researchteamMolecular mechanisms of cell cycle regulationen_US
dc.contributor.icrauthorAlfieri, Claudioen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record