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From Proteopedia
Crystal Structure of Full-Length Human IFIT5 with 5`-triphosphate Oligoadenine
Structural highlights
Function[IFIT5_HUMAN] Interferon-induced RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner. Also recognizes and binds tRNAs.[1] [2] Publication Abstract from PubMedInterferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize viral RNA bearing a 5'-triphosphate group (PPP-RNA), which is a molecular signature that distinguishes it from host RNA. Here we report crystal structures of human IFIT5, its complex with PPP-RNAs, and an amino-terminal fragment of IFIT1. The structures reveal a new helical domain that houses a positively charged cavity designed to specifically engage only single-stranded PPP-RNA, thus distinguishing it from the canonical cytosolic sensor of double-stranded viral PPP-RNA, retinoic acid-inducible gene I (RIG-I, also known as DDX58). Mutational analysis, proteolysis and gel-shift assays reveal that PPP-RNA is bound in a non-sequence-specific manner and requires a 5'-overhang of approximately three nucleotides. Abrogation of PPP-RNA binding in IFIT1 and IFIT5 was found to cause a defect in the antiviral response by human embryonic kidney cells. These results demonstrate the mechanism by which IFIT proteins selectively recognize viral RNA, and lend insight into their downstream effector function. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins.,Abbas YM, Pichlmair A, Gorna MW, Superti-Furga G, Nagar B Nature. 2013 Jan 13. doi: 10.1038/nature11783. PMID:23334420[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Abbas, Y M | Gorna, M W | Nagar, B | Pichlmair, A | Superti-Furga, G | Antiviral | Rna | Rna binding | Rna binding protein-rna complex | Tpr
