Structural insights into the degradation of Mcl-1 induced by BH3 domains
Structural insights into the degradation of Mcl-1 induced by BH3 domains
复制标题
DOI：
10.1073/pnas.0701297104
复制
发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Colman, Peter M.
中科院分区：
文献类型：
--
作者：
Czabotar, Peter E.;Lee, Erinna F.;Colman, Peter M.
细胞凋亡由Bcl-2家族的促生存蛋白控制。远亲的BH 3-only蛋白结合并拮抗它们，从而促进细胞凋亡。而BH 3-唯一的蛋白Noxa的结合，以促生存Mcl-1诱导Mcl-1降解的蛋白酶体，另一个BH 3-唯一的配体，Bim的结合，提高Mcl-1蛋白水平。我们比较了Bim和Noxa的BH 3肽之间形成的复合物的三维结构，并且我们表明Noxa BH 3的离散C-末端序列是煽动Mcl-1降解所必需的。
Apoptosis is held in check by prosurvival proteins of the Bcl-2 family. The distantly related BH3-only proteins bind to and antagonize them, thereby promoting apoptosis. Whereas binding of the BH3-only protein Noxa to prosurvival Mcl-1 induces Mcl-1 degradation by the proteasome, binding of another BH3-only ligand, Bim, elevates Mcl-1 protein levels. We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation.