4g1t
From Proteopedia
Crystal structure of interferon-stimulated gene 54
Structural highlights
FunctionIFIT2_HUMAN IFN-induced antiviral protein which inhibits expression of viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose 2'-O-methylation would provide a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Binds AU-rich viral RNAs, with or without 5' triphosphorylation, RNA-binding is required for antiviral activity. Can promote apoptosis.[1] Publication Abstract from PubMedInterferon-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.Cell Research advance online publication 24 July 2012; doi:10.1038/cr.2012.111. Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms.,Yang Z, Liang H, Zhou Q, Li Y, Chen H, Ye W, Chen D, Fleming J, Shu H, Liu Y Cell Res. 2012 Jul 24. doi: 10.1038/cr.2012.111. PMID:22825553[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Chen D | Chen H | Fleming J | Li Y | Liang H | Liu Y | Shu H | Yang Z | Ye W | Zhou Q