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

Shuyan Duan; Wenqing Gao; Zijun Chen; Zhengyang Li; Suhua Li; Jianhua Gan; Xiangjun Chen; Jixi Li

doi:10.1016/j.biocel.2020.105744

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

Int J Biochem Cell Biol. 2020 May:122:105744. doi: 10.1016/j.biocel.2020.105744. Epub 2020 Mar 29.

Authors

Shuyan Duan¹, Wenqing Gao¹, Zijun Chen¹, Zhengyang Li¹, Suhua Li¹, Jianhua Gan¹, Xiangjun Chen², Jixi Li³

Affiliations

¹ State Key Laboratory of Genetic Engineering, Department of Neurology, School of Life Sciences and Huashan Hospital, Fudan University, Shanghai, 200438, China.
² Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
³ State Key Laboratory of Genetic Engineering, Department of Neurology, School of Life Sciences and Huashan Hospital, Fudan University, Shanghai, 200438, China. Electronic address: lijixi@fudan.edu.cn.

PMID: 32234548
DOI: 10.1016/j.biocel.2020.105744

Abstract

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.

Keywords: Crystal structure; Human archease; RTCB.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
Humans
RNA Ligase (ATP) / chemistry*
RNA Ligase (ATP) / metabolism
RNA-Binding Proteins / chemistry*
RNA-Binding Proteins / metabolism
Transfection

Substances

RNA-Binding Proteins
ZBTB8OS protein, human
tRNA splicing ligase
RNA Ligase (ATP)