Crystal structure of human archease, a key cofactor of tRNA splicing ligase complex.

Crystal structure of human archease, a key cofactor of tRNA splicing ligase complex.
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人类古酶的晶体结构,它是 tRNA 剪接连接酶复合物的关键辅助因子。

DOI:
10.1016/j.biocel.2020.105744
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发表时间:
2020-03
期刊:
Int J Biochem Cell Biol
影响因子:
--
通讯作者:
Li Jixi
Li Jixi
中科院分区:
其他
文献类型:
--
作者:
Duan Shuyan;Gao Wenqing;Chen Zijun;Li Zhengyang;Li Suhua;Gan Jianhua;Chen Xiangjun;Li Jixi

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人类ARCHE,以下称为HARCH,被认为是tRNA-剪接连接酶复合体的关键辅助因子,并且是治疗神经系统损伤的潜在治疗靶点。然而,HARCH在tRNA成熟、mRNA剪接和RNA修复中的结构基础尚不清楚。本文报道了HARCH及其两个突变体D51A和D178A的晶体结构。HARCH由一个延伸的N-末端突出结构域(NTD)和一个紧凑的C-末端结构域(CTD)组成。与以前报道的同源蛋白质不同,第一个亚基的NTD与第二个亚基的CTD相互作用,这种相互作用对维持蛋白质的稳定性可能是重要的。此外,HARCH与细胞内的RNA连接酶RTCB相互作用和共定位。我们目前的研究揭示了HARCH的原子结构,并可能有助于我们理解它在mRNA剪接中的功能。
The human archease, hereafter named HArch, is identified as a key cofactor of the tRNA-splicing ligase complex, and a potential therapeutic target for treating nervous system injuries. However, little is known about the structural basis of HArch in tRNA maturation, mRNA splicing, and RNA repair. Here we report the crystal structures of HArch and its two mutants D51A and D178A with resolutions ranging from 1.96 Å to 3.4 Å. HArch is composed of an extended N-terminal protrusion domain (NTD) and one compacted C-terminal domain (CTD). Unlike previously reported homologous proteins, the NTD of the first subunit interacts with the CTD of the second one, and this interaction might be important for maintaining protein stability. Moreover, HArch interacts and colocalizes with RNA ligase RTCB in cells. Our current study reveals the atomic structure of HArch and may help us understand its function in mRNA splicing.
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