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

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.

SUBMITTER: Herzog F

PROVIDER: S-EPMC2989460 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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

Herzog Franz F Primorac Ivana I Dube Prakash P Lenart Peter P Sander Björn B Mechtler Karl K Stark Holger H Peters Jan-Michael JM

Science (New York, N.Y.) 20090301 5920

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 ...[more]

PMID: 19286556

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