Structural and functional insights into the E3 ligase, RNF126.
Structural and functional insights into the E3 ligase, RNF126.
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DOI：
10.1038/srep26433
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发表时间：
2016-05-19
影响因子：
4.6
通讯作者：
Isaacson RL
中科院分区：
文献类型：
--
作者：
Krysztofinska EM;Martínez-Lumbreras S;Thapaliya A;Evans NJ;High S;Isaacson RL
RNF126是一种E3泛素连接酶，它与BAG6分选酶复合物协同作用，使细胞质中的疏水底物泛素化，这些底物最终被蛋白酶体回收利用。BAG6分选酶由BAG6、TRC35和UBL4A的三聚体复合物组成，它还与SGTA相关，SGTA是一种共同伴侣，它可以从中获得疏水底物。本文求解了RNF126锌指结构域与BAG6 UBL结构域复合物的溶液结构。我们还描述了RNF126和UBL4A之间的相互作用，并分析了SGTA和RNF126之间对n端BAG6结合位点的竞争。这项工作揭示了BAG6复合物及其附属蛋白的分选机制，它们共同决定了水性细胞质中疏水蛋白的命运。
RNF126 is an E3 ubiquitin ligase that collaborates with the BAG6 sortase complex to ubiquitinate hydrophobic substrates in the cytoplasm that are destined for proteasomal recycling. Composed of a trimeric complex of BAG6, TRC35 and UBL4A the BAG6 sortase is also associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Here we solve the solution structure of the RNF126 zinc finger domain in complex with the BAG6 UBL domain. We also characterise an interaction between RNF126 and UBL4A and analyse the competition between SGTA and RNF126 for the N-terminal BAG6 binding site. This work sheds light on the sorting mechanism of the BAG6 complex and its accessory proteins which, together, decide the fate of stray hydrophobic proteins in the aqueous cytoplasm.