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Structure of the Anaphase-Promoting Complex/Cyclosome Interacting with a Mitotic Checkpoint Complex

2009; American Association for the Advancement of Science; Volume: 323; Issue: 5920 Linguagem: Inglês

10.1126/science.1163300

1095-9203

Franz Herzog, Ivana Primorac, Prakash Dube, Péter Lénárt, Bjoern Sander, Karl Mechtler, Holger Stark, Jan‐Michael Peters,

Plant Molecular Biology Research

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.