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

被引：181

作者：

Herzog, Franz ^{[2
]}

Primorac, Ivana ^{[2
]}

Dube, Prakash ^{[1
]}

Lenart, Peter ^{[3
]}

Sander, Bjoern ^{[1
]}

Mechtler, Karl ^{[2
]}

Stark, Holger ^{[1
]}

Peters, Jan-Michael ^{[2
]}

机构：

[1] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany

[2] Res Inst Mol Pathol, A-1030 Vienna, Austria

[3] European Mol Biol Lab, D-69117 Heidelberg, Germany

来源：

SCIENCE | 2009年 / 323卷 / 5920期

基金：

奥地利科学基金会;

关键词：

SPINDLE ASSEMBLY CHECKPOINT; DESTRUCTION BOX; BUDDING YEAST; PROTEIN MAD2; AURORA-B; APC/C; CDC20; INHIBITION; MITOSIS; BUBR1;

D O I：

10.1126/science.1163300

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1477 / 1481

页数：5

共 28 条

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