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PMID: 19286556 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex.

Science (New York, N.Y.) ·Vol. 323 ·No. 5920 ·2009-03-13 ·Pages 1477-81

Herzog F, Primorac I, Dube P, Lenart P, Sander B, Mechtler K, Stark H, Peters JM

Abstract

Once all chromosomes are connected to the mitotic spindle (bioriented), anaphase is initiated by the protein ubiquitylation activity of the anaphase-promoting complex/cyclosome (APC/C) and its coactivator Cdc20 (APC/C(Cdc20)). Before chromosome biorientation, anaphase is delayed by a mitotic checkpoint complex (MCC) that inhibits APC/C(Cdc20). We used single-particle electron microscopy to obtain three-dimensional models of human APC/C in various functional states: bound to MCC, to Cdc20, or to neither (apo-APC/C). These experiments revealed that MCC associates with the Cdc20 binding site on APC/C, locks the otherwise flexible APC/C in a "closed" state, and prevents binding and ubiquitylation of a wide range of different APC/C substrates. These observations clarify the structural basis for the inhibition of APC/C by spindle checkpoint proteins.

MeSH Terms
Anaphase Anaphase-Promoting Complex-Cyclosome Cdc20 Proteins Cell Cycle Proteins/chemistry,metabolism HeLa Cells Humans Image Processing, Computer-Assisted Imaging, Three-Dimensional Microscopy, Electron Mitosis Models, Molecular Protein Binding Protein Conformation Protein Structure, Tertiary Spindle Apparatus/metabolism Ubiquitin-Conjugating Enzymes/chemistry,metabolism Ubiquitin-Protein Ligase Complexes/chemistry,metabolism Ubiquitination
Chemicals
Cdc20 Proteins Cell Cycle Proteins CDC20 protein, human UBE2C protein, human Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Herzog Franz
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
Primorac Ivana
Dube Prakash
Lenart Peter
Sander Björn
Mechtler Karl
Stark Holger
Peters Jan-Michael
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28 references, click to expand
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1163300
Published
2009-03-13
Pages
1477-81
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2989460
Subset
IM
Grants
Austrian Science Fund FWF · F 3407 · Austria
External Links
PubMed source DOI: 10.1126/science.1163300 PMC Full Text View journal details
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