Crystal structure and nucleotide selectivity of human IFIT5/ISG58

Dear editor, Interferon-stimulated gene 56 （ISG56） family mem- bers, ISG56, ISG54, ISG58 and ISG60, also known as interferon-induced protein with tetratricopeptide repeats （TPR） 1 （IFIT1）, IFIT2, IFIT5 and IFIT3, respectively, play crucial roles in human antiviral defense systems. Recent studies have shown that ISG56 specifically rec- ognizes viral 5＇-pppRNA [1]. Using structural biology methods, we found that ISG54 possesses a right-handed helical channel in its C-terminal region, which recogniz- es AU-rich RNAs [2]. ISG54 mutants whose nucleotide- binding sites were destroyed showed a significant loss of their antiviral activities [2]. As the expression patterns of ISG56 family proteins have been reported to be cell- and inducer-specific [3], we hypothesize that different ISG56 family members likely recognize distinct substrates.