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PDBsum entry 4hos
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RNA binding protein/RNA
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PDB id
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4hos
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References listed in PDB file
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Key reference
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Title
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Structural basis for viral 5'-Ppp-Rna recognition by human ifit proteins.
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Authors
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Y.M.Abbas,
A.Pichlmair,
M.W.GóRNA,
G.Superti-Furga,
B.Nagar.
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Ref.
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Nature, 2013,
494,
60-64.
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PubMed id
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Abstract
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Interferon-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.
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