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| | ==The Structure of human Argonaute-1 in complex with the hook motif of human GW182== | | ==The Structure of human Argonaute-1 in complex with the hook motif of human GW182== |
| - | <StructureSection load='5w6v' size='340' side='right' caption='[[5w6v]], [[Resolution|resolution]] 2.83Å' scene=''> | + | <StructureSection load='5w6v' size='340' side='right'caption='[[5w6v]], [[Resolution|resolution]] 2.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w6v]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W6V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W6V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w6v]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W6V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W6V FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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]] 2.828Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGO1, EIF2C1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TNRC6A, CAGH26, KIAA1460, TNRC6 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5w6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w6v OCA], [https://pdbe.org/5w6v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w6v RCSB], [https://www.ebi.ac.uk/pdbsum/5w6v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w6v ProSAT]</span></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=5w6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w6v OCA], [http://pdbe.org/5w6v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w6v RCSB], [http://www.ebi.ac.uk/pdbsum/5w6v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w6v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AGO1_HUMAN AGO1_HUMAN]] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).<ref>PMID:16289642</ref> <ref>PMID:16936728</ref> <ref>PMID:18771919</ref> [[http://www.uniprot.org/uniprot/TNR6A_HUMAN TNR6A_HUMAN]] Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As scaffoldng protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes.<ref>PMID:16284622</ref> <ref>PMID:16284623</ref> <ref>PMID:17596515</ref> <ref>PMID:17671087</ref> <ref>PMID:19056672</ref> <ref>PMID:19304925</ref> | + | [https://www.uniprot.org/uniprot/AGO1_HUMAN AGO1_HUMAN] Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).<ref>PMID:16289642</ref> <ref>PMID:16936728</ref> <ref>PMID:18771919</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5w6v" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5w6v" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Argonaute 3D structures|Argonaute 3D structures]] |
| | + | *[[Eukaryotic initiation factor 3D structures|Eukaryotic initiation factor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Spodoptera frugiperda]] | | [[Category: Spodoptera frugiperda]] |
| - | [[Category: Elkayam, E]] | + | [[Category: Elkayam E]] |
| - | [[Category: Faehnle, C R]] | + | [[Category: Faehnle CR]] |
| - | [[Category: Joshua-Tor, L]] | + | [[Category: Joshua-Tor L]] |
| - | [[Category: Gene regulation-rna complex]]
| + | |
| - | [[Category: Gw motif]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Rna interference]]
| + | |
| Structural highlights
Function
AGO1_HUMAN Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).[1] [2] [3]
Publication Abstract from PubMed
In miRNA-mediated gene silencing, the physical interaction between human Argonaute (hAgo) and GW182 (hGW182) is essential for facilitating the downstream silencing of the targeted mRNA. GW182 can interact with hAgo via three of the GW/WG repeats in its Argonaute-binding domain: motif-1, motif-2, and the hook motif. The structure of hAgo1 in complex with the hook motif of hGW182 reveals a "gate"-like interaction that is critical for GW182 docking into one of hAgo1's tryptophan-binding pockets. We show that hAgo1 and hAgo2 have a single GW182-binding site and that miRNA binding increases hAgo's affinity to GW182. With target binding occurring rapidly, this ensures that only mature RISC would be recruited for silencing. Finally, we show that hGW182 can recruit up to three copies of hAgo via its three GW motifs. This may explain the observed cooperativity in miRNA-mediated gene silencing.
Multivalent Recruitment of Human Argonaute by GW182.,Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, Tuschl T. Identification of novel argonaute-associated proteins. Curr Biol. 2005 Dec 6;15(23):2149-55. Epub 2005 Nov 10. PMID:16289642 doi:10.1016/j.cub.2005.10.048
- ↑ Janowski BA, Huffman KE, Schwartz JC, Ram R, Nordsell R, Shames DS, Minna JD, Corey DR. Involvement of AGO1 and AGO2 in mammalian transcriptional silencing. Nat Struct Mol Biol. 2006 Sep;13(9):787-92. Epub 2006 Aug 27. PMID:16936728 doi:nsmb1140
- ↑ Wu L, Fan J, Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. 2008 Sep 9;18(17):1327-32. doi: 10.1016/j.cub.2008.07.072. PMID:18771919 doi:10.1016/j.cub.2008.07.072
- ↑ Elkayam E, Faehnle CR, Morales M, Sun J, Li H, Joshua-Tor L. Multivalent Recruitment of Human Argonaute by GW182. Mol Cell. 2017 Aug 17;67(4):646-658.e3. doi: 10.1016/j.molcel.2017.07.007. Epub, 2017 Aug 3. PMID:28781232 doi:http://dx.doi.org/10.1016/j.molcel.2017.07.007
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