The Structure and Ubiquitin Binding Properties of TRAF RING Heterodimers
The Structure and Ubiquitin Binding Properties of TRAF RING Heterodimers
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DOI：
10.1016/j.jmb.2021.166844
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发表时间：
2021-02-20
影响因子：
5.6
通讯作者：
Day, Catherine L.
中科院分区：
文献类型：
--
作者：
Das, Anubrita;Middleton, Adam J.;Day, Catherine L.
肿瘤坏死因子（TNF）受体相关因子（TRAF）家族成员具有共同的结构域结构，但在细胞信号传导中发挥非冗余的生理作用。在N末端，大多数TRAF具有RING结构域，随后是一系列锌指（ZF）结构域。TRAF 6的RING结构域二聚化，并且RING同二聚体与第一ZF一起组装形成促进下游激酶活化的平台的泛素链。环二聚体界面是保守的TRAF蛋白，这表明功能异源二聚体可能是可能的。在这里，我们报告的TRAF 5-TRAF 6环异二聚体的结构，这占的异二聚体的稳定性，以及其组装泛素链的能力。我们还发现TRAF 6的RING结构域与TRAF 3和TRAF 2异源二聚化，并证明TRAF 2的接头螺旋和第一ZF可以与TRAF 6合作以促进链组装。总的来说，我们的研究结果表明，TRAF环同源和异源二聚体有可能桥接附近的TRAF三聚体的相互作用和调节TRAF介导的信号。(C)2021爱思唯尔有限公司保留所有权利。
Tumour necrosis factor (TNF) receptor associated factor (TRAF) family members share a common domain architecture, but play non-redundant physiological roles in cell signalling. At the N terminus, most TRAFs have a RING domain, followed by a series of Zinc finger (ZF) domains. The RING domain of TRAF6 dimerizes, and the RING homodimer together with the first ZF assembles ubiquitin chains that form a platform which facilitates activation of downstream kinases. The RING dimer interface is conserved amongst TRAF proteins, suggesting that functional heterodimers could be possible. Here we report the structure of the TRAF5-TRAF6 RING heterodimer, which accounts for the stability of the heterodimer as well as its ability to assemble ubiquitin chains. We also show that the RING domain of TRAF6 heterodimerizes with TRAF3 and TRAF2, and demonstrate that the linker helix and first ZF of TRAF2 can cooperate with TRAF6 to promote chain assembly. Collectively our results suggest that TRAF RING homo- and hetero-dimers have the potential to bridge interaction of nearby TRAF trimers and modulate TRAF-mediated signalling. (C) 2021 Elsevier Ltd. All rights reserved.