TRIM56 coiled-coil domain structure provides insights into its E3 ligase functions.

TRIM56 coiled-coil domain structure provides insights into its E3 ligase functions.
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DOI:
10.1016/j.csbj.2023.04.022
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发表时间:
2023
影响因子:
6
通讯作者:
Li, Xian C.
Li, Xian C.
中科院分区:
生物学2区
文献类型:
--
作者:
Lou, Xiaohua;Ma, Binbin;Zhuang, Yuan;Xiao, Xiang;Minze, Laurie J.;Xing, Junji;Zhang, Zhiqiang;Li, Xian C.

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蛋白质泛素化是由E3泛素连接酶介导的翻译后修饰。RING结构域E3连接酶是最大的E3泛素连接酶家族,它们充当支架,将E2-泛素复合物及其底物结合在一起以促进直接泛素转移。然而,执行泛素转移的RING E3连接酶的四级结构仍然知之甚少。在这项研究中,我们解决了TRIM 56的晶体结构,RING E3连接酶的成员。卷曲螺旋结构域的结构表明,两个反平行的二聚体结合在一起,形成一个四聚体在一个小的交叉角。这种四聚体结构允许两个RING结构域存在于每一侧,以形成活性同源二聚体,支持泛素从E2转移到其附近的底物,该底物由同一侧的C-末端结构域募集。这些发现表明,卷曲螺旋结构域介导的四聚体是一个可行的支架,促进泛素的招聘和转移,以实现E3连接酶的活性。
Protein ubiquitination is a post-translation modification mediated by E3 ubiquitin ligases. The RING domain E3 ligases are the largest family of E3 ubiquitin ligases, they act as a scaffold, bringing the E2-ubiquitin complex and its substrate together to facilitate direct ubiquitin transfer. However, the quaternary structures of RING E3 ligases that perform ubiquitin transfer remain poorly understood. In this study, we solved the crystal structure of TRIM56, a member of the RING E3 ligase. The structure of the coiled-coil domain indicated that the two anti-parallel dimers bound together to form a tetramer at a small crossing angle. This tetramer structure allows two RING domains to exist on each side to form an active homodimer in supporting ubiquitin transfer from E2 to its nearby substrate recruited by the C-terminal domains on the same side. These findings suggest that the coiled-coil domain-mediated tetramer is a feasible scaffold for facilitating the recruitment and transfer of ubiquitin to accomplish E3 ligase activity.
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