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| | ==Crystal Structure of N-terminal Human IFIT1== | | ==Crystal Structure of N-terminal Human IFIT1== |
| - | <StructureSection load='4hou' size='340' side='right' caption='[[4hou]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4hou' size='340' side='right'caption='[[4hou]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hou]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HOU FirstGlance]. <br> | + | <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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hos|4hos]], [[4hot|4hot]], [[4hoq|4hoq]], [[4hop|4hop]]</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> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">G10P1, IFI56, IFIT1, IFIT1/ISG56, IFNAI1, ISG56 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hou OCA], [http://pdbe.org/4hou PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hou RCSB], [http://www.ebi.ac.uk/pdbsum/4hou PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hou ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Abbas, Y M]] | + | [[Category: Large Structures]] |
| - | [[Category: Gorna, M W]] | + | [[Category: Abbas YM]] |
| - | [[Category: Nagar, B]] | + | [[Category: Gorna MW]] |
| - | [[Category: Pichlmair, A]] | + | [[Category: Nagar B]] |
| - | [[Category: Superti-Furga, G]] | + | [[Category: Pichlmair A]] |
| - | [[Category: Antiviral]]
| + | [[Category: Superti-Furga G]] |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Rna binding]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Tpr]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
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[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Terenzi F, Saikia P, Sen GC. Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1. EMBO J. 2008 Dec 17;27(24):3311-21. doi: 10.1038/emboj.2008.241. Epub 2008 Nov, 13. PMID:19008854 doi:http://dx.doi.org/10.1038/emboj.2008.241
- ↑ Li Y, Li C, Xue P, Zhong B, Mao AP, Ran Y, Chen H, Wang YY, Yang F, Shu HB. ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7945-50. doi:, 10.1073/pnas.0900818106. Epub 2009 Apr 28. PMID:19416887 doi:http://dx.doi.org/10.1073/pnas.0900818106
- ↑ Raychoudhuri A, Shrivastava S, Steele R, Kim H, Ray R, Ray RB. ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. J Virol. 2011 Dec;85(24):12881-9. doi: 10.1128/JVI.05633-11. Epub 2011 Oct 5. PMID:21976647 doi:http://dx.doi.org/10.1128/JVI.05633-11
- ↑ Abbas YM, Pichlmair A, Gorna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature. 2013 Jan 13. doi: 10.1038/nature11783. PMID:23334420 doi:http://dx.doi.org/10.1038/nature11783
- ↑ Abbas YM, Pichlmair A, Gorna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature. 2013 Jan 13. doi: 10.1038/nature11783. PMID:23334420 doi:http://dx.doi.org/10.1038/nature11783
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