Crystal structure of human archease, a key cofactor of tRNA splicing ligase complex. (May 2020)

• Record Type: Journal Article
• Authors: Duan, Shuyan; Gao, Wenqing; Chen, Zijun; Li, Zhengyang; Li, Suhua; Gan, Jianhua; Chen, Xiangjun; Li, Jixi
• Is Part Of: International journal of biochemistry & cell biology. Volume 122(2020)
• Publication Date: 2020-05
• Subjects: Human archease -- Crystal structure -- RTCB; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2020.105744
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: The crystal structure of the HArch was revealed. The NTD of the HArch is significantly different from its homologous proteins. HArch interacts and colocalizes with RNA ligase RTCB in cells. 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.