dc.contributor.author | da Fonseca, PCA | |
dc.contributor.author | Kong, EH | |
dc.contributor.author | Zhang, Z | |
dc.contributor.author | Schreiber, A | |
dc.contributor.author | Williams, MA | |
dc.contributor.author | Morris, EP | |
dc.contributor.author | Barford, D | |
dc.date.accessioned | 2018-08-02T13:53:20Z | |
dc.date.issued | 2011-02-10 | |
dc.identifier.citation | Nature, 2011, 470 (7333), pp. 274 - 278 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2244 | |
dc.identifier.eissn | 1476-4687 | |
dc.identifier.doi | 10.1038/nature09625 | |
dc.description.abstract | The ubiquitylation of cell-cycle regulatory proteins by the large multimeric anaphase-promoting complex (APC/C) controls sister chromatid segregation and the exit from mitosis. Selection of APC/C targets is achieved through recognition of destruction motifs, predominantly the destruction (D)-box and KEN (Lys-Glu-Asn)-box. Although this process is known to involve a co-activator protein (either Cdc20 or Cdh1) together with core APC/C subunits, the structural basis for substrate recognition and ubiquitylation is not understood. Here we investigate budding yeast APC/C using single-particle electron microscopy and determine a cryo-electron microscopy map of APC/C in complex with the Cdh1 co-activator protein (APC/C(Cdh1)) bound to a D-box peptide at ∼10 Å resolution. We find that a combined catalytic and substrate-recognition module is located within the central cavity of the APC/C assembled from Cdh1, Apc10--a core APC/C subunit previously implicated in substrate recognition--and the cullin domain of Apc2. Cdh1 and Apc10, identified from difference maps, create a co-receptor for the D-box following repositioning of Cdh1 towards Apc10. Using NMR spectroscopy we demonstrate specific D-box-Apc10 interactions, consistent with a role for Apc10 in directly contributing towards D-box recognition by the APC/C(Cdh1) complex. Our results rationalize the contribution of both co-activator and core APC/C subunits to D-box recognition and provide a structural framework for understanding mechanisms of substrate recognition and catalysis by the APC/C. | |
dc.format | Print-Electronic | |
dc.format.extent | 274 - 278 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Saccharomyces cerevisiae | |
dc.subject | Ubiquitin-Protein Ligase Complexes | |
dc.subject | Peptides | |
dc.subject | Cell Cycle Proteins | |
dc.subject | Saccharomyces cerevisiae Proteins | |
dc.subject | Cryoelectron Microscopy | |
dc.subject | Nuclear Magnetic Resonance, Biomolecular | |
dc.subject | Amino Acid Motifs | |
dc.subject | Protein Conformation | |
dc.subject | Protein Binding | |
dc.subject | Substrate Specificity | |
dc.subject | Models, Molecular | |
dc.subject | Ubiquitination | |
dc.subject | Biocatalysis | |
dc.subject | Anaphase-Promoting Complex-Cyclosome | |
dc.subject | Cdh1 Proteins | |
dc.subject | Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome | |
dc.subject | Apc10 Subunit, Anaphase-Promoting Complex-Cyclosome | |
dc.title | Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2010-11-01 | |
rioxxterms.versionofrecord | 10.1038/nature09625 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2011-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature | |
pubs.issue | 7333 | |
pubs.notes | Not known | |
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/Structural Electron Microscopy | |
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/Structural Electron Microscopy | |
pubs.publication-status | Published | |
pubs.volume | 470 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Structural Electron Microscopy | |
dc.contributor.icrauthor | da Fonseca, Paula Cristina Alves | |
dc.contributor.icrauthor | Morris, Edward | |