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| | ==Structure of Human Argonaute-1 let-7 complex== | | ==Structure of Human Argonaute-1 let-7 complex== |
| - | <StructureSection load='4krf' size='340' side='right' caption='[[4krf]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4krf' size='340' side='right'caption='[[4krf]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4krf]] 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=4KRF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KRF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4krf]] 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=4KRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KRF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kre|4kre]]</td></tr> | + | </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=4krf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4krf OCA], [https://pdbe.org/4krf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4krf RCSB], [https://www.ebi.ac.uk/pdbsum/4krf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4krf ProSAT]</span></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])</td></tr>
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| - | <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=4krf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4krf OCA], [http://pdbe.org/4krf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4krf RCSB], [http://www.ebi.ac.uk/pdbsum/4krf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4krf 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> | + | [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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| | ==See Also== | | ==See Also== |
| - | *[[Argonaute|Argonaute]] | + | *[[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: Elkayam, E]] | + | [[Category: Large Structures]] |
| - | [[Category: Faehnle, C R]] | + | [[Category: Elkayam E]] |
| - | [[Category: Joshua-Tor, L]] | + | [[Category: Faehnle CR]] |
| - | [[Category: Eukaryotic argonaute]] | + | [[Category: Joshua-Tor L]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[Category: Rnai]]
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| - | [[Category: Slicer]]
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| - | [[Category: Transcription-rna complex]]
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| 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
Argonautes are the central protein component in small RNA silencing pathways. Of the four human Argonautes (hAgo1-hAgo4) only hAgo2 is an active slicer. We determined the structure of hAgo1 bound to endogenous copurified RNAs to 1.75 A resolution and hAgo1 loaded with let-7 microRNA to 2.1 A. Both structures are strikingly similar to the structures of hAgo2. A conserved catalytic tetrad within the PIWI domain of hAgo2 is required for its slicing activity. Completion of the tetrad, combined with a mutation on a loop adjacent to the active site of hAgo1, results in slicer activity that is substantially enhanced by swapping in the N domain of hAgo2. hAgo3, with an intact tetrad, becomes an active slicer by swapping the N domain of hAgo2 without additional mutations. Intriguingly, the elements that make Argonaute an active slicer involve a sophisticated interplay between the active site and more distant regions of the enzyme.
The making of a slicer: activation of human argonaute-1.,Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L Cell Rep. 2013 Jun 27;3(6):1901-9. doi: 10.1016/j.celrep.2013.05.033. Epub 2013, Jun 6. PMID:23746446[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
- ↑ Faehnle CR, Elkayam E, Haase AD, Hannon GJ, Joshua-Tor L. The making of a slicer: activation of human argonaute-1. Cell Rep. 2013 Jun 27;3(6):1901-9. doi: 10.1016/j.celrep.2013.05.033. Epub 2013, Jun 6. PMID:23746446 doi:10.1016/j.celrep.2013.05.033
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