Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms  

作　　者：Zhenlin Yang Huanhuan Liang Qian Zhou Ying Li Haiwei Chen Wen Ye Danying Chen Joy Fleming Hongbing Shu Yingfang Liu 

机构地区：[1]State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaovang District, Beijing 100101, China [2]College of Life Sciences, Wuhan University, Luojia Hill, Wuhan, Hubei 430072, China [3]School of Life Sciences, Peking University 5 Yi He Yuan Road, Haidian, Beijing 100871, China

出　　处：《Cell Research》2012年第9期1328-1338,共11页细胞研究（英文版）

基　　金：We thank our colleagues Drs Hongfei Wang and Lijie Wu for crystal data collection. We thank Yuanyuan Chert and Xiaoxia Yu in core facility center （Institute of Biophysics, CAS） for technical assistance with the ITC, SPR and ultra-centrifugation experiments. We thank colleagues at the Photon factory, KEK （Japan） and SSRF （China） for assistance in the use of the synchrotron resource. We also thank Drs Xiufan Liu and Shunlin Hu （Yangzhou University） for providing the cDNA of ZJ1-NDV. This work was supported by grants to YL from the Ministry of Science and Technology （863 Project 2006AAO2A314; 973 Programs 2007CB914303, 2011CB910304 and 2012CB9 10204） and the National Natural Science Foundation of China （30925011, 31030024 and 31021062）.

摘　　要：Interferon-stimulated gene 56 （ISG56） family members play important roles in blocking viral replication and regulating cellular functions, however, their underlying molecular mechanisms are largely unclear. Here, we present the crystal structure of ISG54, an ISG56 family protein with a novel RNA-hinding structure. The structure shows that ISG54 monomers have 9 tetratricopeptide repeat-like motifs and associate to form domain-swapped dimers. The Cterminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface. EMSA results show that ISG54 binds specifically to some RNAs, such as adenylate uridylate （AU）-rich RNAs, with or without 5＇ triphosphorylation. Mutagenesis and functional studies show that this RNA- binding ability is important to its antiviral activity. Our results suggest a new mechanism underlying the antiviral activity of this interferon-inducible gene 56 family member.

关 键 词：structure biology ISG54 

分 类 号：Q255[生物学—细胞生物学] O614.121[理学—无机化学]