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

Abstract

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-binding structure. The structure shows that ISG54 monomers have 9 tetratricopeptide repeat-like motifs and associate to form domain-swapped dimers. The C-terminal 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.

DOI: 10.1038/cr.2012.111

Cite this paper

@article{Yang2012CrystalSO, title={Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms.}, author={Zhenlin Yang and Huanhuan Liang and Qian Zhou and Ying Li and Haiwei Chen and Wen Ye and Danying Chen and Joy Fleming and Hong-Bing Shu and Yingfang Liu}, journal={Cell research}, year={2012}, volume={22 9}, pages={1328-38} }