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

Franz Herzog, Ivana Primorac, Prakash Dube, Peter Lenart, Björn Sander, Karl Mechtler, Holger Stark, Jan Michael Peters

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

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/CCdc20). Before chromosome biorientation, anaphase is delayed by a mitotic checkpoint complex (MCC) that inhibits APC/CCdc20. 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.

OriginalspracheEnglisch
Seiten (von - bis)1477-1481
Seitenumfang5
FachzeitschriftScience
Jahrgang323
Ausgabenummer5920
DOIs
PublikationsstatusVeröffentlicht - 13 März 2009
Extern publiziertJa

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