View source for 4hou


==Crystal Structure of N-terminal Human IFIT1==
<StructureSection load='4hou' size='340' side='right'caption='[[4hou]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hou]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HOU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HOU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hou OCA], [https://pdbe.org/4hou PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hou RCSB], [https://www.ebi.ac.uk/pdbsum/4hou PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hou ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IFIT1_HUMAN IFIT1_HUMAN] Interferon-induced antiviral 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 and inhibiting expression of viral messenger 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. 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). Exhibits antiviral activity against several viruses including human papilloma and hepatitis C viruses.<ref>PMID:19008854</ref> <ref>PMID:19416887</ref> <ref>PMID:21976647</ref> <ref>PMID:23334420</ref> 
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:23334420</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4hou" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Abbas YM]]
[[Category: Gorna MW]]
[[Category: Nagar B]]
[[Category: Pichlmair A]]
[[Category: Superti-Furga G]]