Structural Basis for Substrate Selectivity of the E3 Ligase COP1.
Structural Basis for Substrate Selectivity of the E3 Ligase COP1.
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DOI：
10.1016/j.str.2016.03.002
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Blacklow SC
中科院分区：
文献类型：
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作者：
Uljon S;Xu X;Durzynska I;Stein S;Adelmant G;Marto JA;Pear WS;Blacklow SC
COP 1蛋白是E3泛素连接酶，调节植物的向光性，并靶向转录因子降解哺乳动物。COP 1的底物结合区位于WD 40重复结构域内，该结构域也与Trib蛋白结合，Trib蛋白是C/EBPα降解的衔接子。我们在这里报告的结构的人COP 1 WD 40域的隔离，和复合物的人和拟南芥COP 1 WD 40域与Trib 1的结合基序。人和拟南芥属WD 40结构域是七叶片β-螺旋桨，在第一叶片的底面上具有插入的环。Trib 1肽以延伸构象结合到β-螺旋桨顶面上的高度保守表面，表明COP 1识别肽基序的一般模式。总之，这些研究确定了COP 1识别基序的结构基础和关键相互作用，并暗示了如何克服Trib 1自身抑制作用以靶向C/EBPα进行降解。
COP1 proteins are E3 ubiquitin ligases that regulate phototropism in plants and target transcription factors for degradation in mammals. The substrate-binding region of COP1 resides within a WD40-repeat domain that also binds to Trib proteins, which are adaptors for C/EBPα degradation. We report here structures of the human COP1 WD40 domain in isolation, and complexes of the human and Arabidopsis thaliana COP1 WD40 domains with the binding motif of Trib1. The human and Arabidopsis WD40 domains are seven-bladed β-propellers with an inserted loop on the bottom face of the first blade. The Trib1 peptide binds in an extended conformation to a highly conserved surface on the top face of the β-propeller, indicating a general mode for recognition of peptide motifs by COP1. Together, these studies identify the structural basis and key interactions for motif recognition by COP1, and hint at how Trib1 autoinhibition is overcome to target C/EBPα for degradation.