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| | <StructureSection load='3u9g' size='340' side='right'caption='[[3u9g]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='3u9g' size='340' side='right'caption='[[3u9g]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u9g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U9G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u9g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U9G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.801Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Zc3hav1, Zap ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3u9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u9g OCA], [https://pdbe.org/3u9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u9g RCSB], [https://www.ebi.ac.uk/pdbsum/3u9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u9g ProSAT]</span></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=3u9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u9g OCA], [https://pdbe.org/3u9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u9g RCSB], [https://www.ebi.ac.uk/pdbsum/3u9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u9g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ZCCHV_RAT ZCCHV_RAT]] Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation.<ref>PMID:12215647</ref> <ref>PMID:14557641</ref> <ref>PMID:17182693</ref> <ref>PMID:17185417</ref> <ref>PMID:17928353</ref> <ref>PMID:18225958</ref> <ref>PMID:21876179</ref>
| + | [https://www.uniprot.org/uniprot/ZCCHV_RAT ZCCHV_RAT] Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation.<ref>PMID:12215647</ref> <ref>PMID:14557641</ref> <ref>PMID:17182693</ref> <ref>PMID:17185417</ref> <ref>PMID:17928353</ref> <ref>PMID:18225958</ref> <ref>PMID:21876179</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses, such as HIV-1, by targeting viral mRNA for degradation. How ZAP recognizes its target RNA has been unclear. Here we report the crystal structure of the N-terminal domain of rat ZAP (NZAP225), the major functional domain. The overall structure of NZAP225 resembles a tractor, with four zinc-finger motifs located at the bottom. Structural and functional analyses identified multiple positively charged residues and two putative RNA-binding cavities forming a large putative RNA-binding cleft. ZAP molecules interact to form a dimer that binds to a ZAP-responsive RNA molecule containing two ZAP-binding modules. These results provide insights into how ZAP binds specifically to complex target RNA.
| + | |
| - | | + | |
| - | Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA.,Chen S, Xu Y, Zhang K, Wang X, Sun J, Gao G, Liu Y Nat Struct Mol Biol. 2012 Mar 11;19(4):430-5. doi: 10.1038/nsmb.2243. PMID:22407013<ref>PMID:22407013</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3u9g" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, S]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Gao, G]] | + | [[Category: Chen S]] |
| - | [[Category: Liu, Y]] | + | [[Category: Gao G]] |
| - | [[Category: Sun, J]] | + | [[Category: Liu Y]] |
| - | [[Category: Wang, X]] | + | [[Category: Sun J]] |
| - | [[Category: Xu, Y]] | + | [[Category: Wang X]] |
| - | [[Category: Zhang, K]] | + | [[Category: Xu Y]] |
| - | [[Category: Antiviral protein]]
| + | [[Category: Zhang K]] |
| - | [[Category: Zinc finger protein]]
| + | |
| Structural highlights
Function
ZCCHV_RAT Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1) and moloney and murine leukemia virus (MoMLV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Gao G, Guo X, Goff SP. Inhibition of retroviral RNA production by ZAP, a CCCH-type zinc finger protein. Science. 2002 Sep 6;297(5587):1703-6. PMID:12215647 doi:http://dx.doi.org/10.1126/science.1074276
- ↑ Bick MJ, Carroll JW, Gao G, Goff SP, Rice CM, MacDonald MR. Expression of the zinc-finger antiviral protein inhibits alphavirus replication. J Virol. 2003 Nov;77(21):11555-62. PMID:14557641
- ↑ Muller S, Moller P, Bick MJ, Wurr S, Becker S, Gunther S, Kummerer BM. Inhibition of filovirus replication by the zinc finger antiviral protein. J Virol. 2007 Mar;81(5):2391-400. Epub 2006 Dec 20. PMID:17182693 doi:http://dx.doi.org/10.1128/JVI.01601-06
- ↑ Guo X, Ma J, Sun J, Gao G. The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):151-6. Epub 2006 Dec 21. PMID:17185417 doi:http://dx.doi.org/10.1073/pnas.0607063104
- ↑ MacDonald MR, Machlin ES, Albin OR, Levy DE. The zinc finger antiviral protein acts synergistically with an interferon-induced factor for maximal activity against alphaviruses. J Virol. 2007 Dec;81(24):13509-18. Epub 2007 Oct 10. PMID:17928353 doi:http://dx.doi.org/10.1128/JVI.00402-07
- ↑ Kerns JA, Emerman M, Malik HS. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet. 2008 Jan;4(1):e21. doi: 10.1371/journal.pgen.0040021. PMID:18225958 doi:http://dx.doi.org/10.1371/journal.pgen.0040021
- ↑ Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, Sun J, Wu L, Zheng YT, Gao G. Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15834-9. doi:, 10.1073/pnas.1101676108. Epub 2011 Aug 29. PMID:21876179 doi:http://dx.doi.org/10.1073/pnas.1101676108
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