Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex.
Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex.
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APC/C共激活因子从ACM1-CDH1复合物的结构中识别DEGRON识别。
DOI：
10.1016/j.molcel.2013.04.024
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发表时间：
2013-06-06
期刊：
影响因子：
16
通讯作者：
Barford, David
中科院分区：
文献类型：
--
作者：
He, Jun;Chao, William C. H.;Zhang, Ziguo;Yang, Jing;Cronin, Nora;Barford, David
后期促进复合体/环体(APC/C)调节姐妹染色单体的分离和有丝分裂的退出。大多数APC/C底物的选择是由与底物破坏基序相互作用的共激活亚基(Cdc20或Cdh1)控制的--主要是破坏(D)盒和Ken盒退化。共激活子如何识别D盒退化以及如何被APC/C调节蛋白抑制，这些都没有在原子水平上定义。在这里，我们从酿酒酵母CDH1与其特异性抑制剂Acm1的晶体结构入手，描述了D box识别的分子基础。Acm1和CDH1之间的额外相互作用确定了CDH1上的第三个蛋白结合位点，该位点可能赋予共激活子特定的蛋白质功能，包括底物结合。我们提供了共激活子识别D盒和Ken盒的结构合理性，并证明了许多非规范的APC/C降解子与D盒共受体结合。与APC/C辅活化子结合的D盒基序的第一结构--D盒和Ken盒共同序列的合理化某些非规范的APC/C简并子被指定为共激活子上简并的D或Ken盒结合位点，用于结合调节蛋白和底物
The anaphase-promoting complex/cyclosome (APC/C) regulates sister chromatid segregation and the exit from mitosis. Selection of most APC/C substrates is controlled by coactivator subunits (either Cdc20 or Cdh1) that interact with substrate destruction motifs—predominantly the destruction (D) box and KEN box degrons. How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory proteins is not defined at the atomic level. Here, from the crystal structure of S. cerevisiae Cdh1 in complex with its specific inhibitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis for D box recognition. Additional interactions between Acm1 and Cdh1 identify a third protein-binding site on Cdh1 that is likely to confer coactivator-specific protein functions including substrate association. We provide a structural rationalization for D box and KEN box recognition by coactivators and demonstrate that many noncanonical APC/C degrons bind APC/C coactivators at the D box coreceptor. First structure of a D box motif bound to an APC/C coactivator Rationalization of D box and KEN box consensus sequences Assignment of some noncanonical APC/C degrons as either degenerate D or KEN boxes Binding site on coactivator for binding regulatory proteins and substrates
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
Evans, P
影响因子：
9.2
作者：
Carroll, CW;Enquist-Newman, M;Morgan, DO
通讯作者：
Morgan, DO
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
11.4
作者：
Burton, Janet L.;Xiong, Yong;Solomon, Mark J.
通讯作者：
Solomon, Mark J.
影响因子：
5.3
作者：
Castro, A;Vigneron, S;Lorca, T
通讯作者：
Lorca, T