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| | ==Structure of human ARGONAUTE1 in complex with guide RNA== | | ==Structure of human ARGONAUTE1 in complex with guide RNA== |
| - | <StructureSection load='4kxt' size='340' side='right' caption='[[4kxt]], [[Resolution|resolution]] 2.29Å' scene=''> | + | <StructureSection load='4kxt' size='340' side='right'caption='[[4kxt]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4kxt]] is a 2 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=4KXT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KXT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4kxt]] is a 2 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=4KXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KXT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2C1, AGO1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxt OCA], [https://pdbe.org/4kxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kxt RCSB], [https://www.ebi.ac.uk/pdbsum/4kxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kxt 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=4kxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxt OCA], [http://pdbe.org/4kxt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kxt RCSB], [http://www.ebi.ac.uk/pdbsum/4kxt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kxt 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: Large Structures]] |
| | [[Category: Spodoptera frugiperda]] | | [[Category: Spodoptera frugiperda]] |
| - | [[Category: Nakanishi, K]] | + | [[Category: Nakanishi K]] |
| - | [[Category: Patel, D J]] | + | [[Category: Patel DJ]] |
| - | [[Category: Hydrolase-rna complex]]
| + | |
| - | [[Category: Nuclease]]
| + | |
| - | [[Category: Rna]]
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| - | [[Category: Rnase h fold]]
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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
We have solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify changes that evolutionarily rendered hAGO1 inactive, we compared our structure with guide-RNA-containing and cleavage-active hAGO2. Aside from mutation of a catalytic tetrad residue, proline residues at positions 670 and 675 in hAGO1 introduce a kink in the cS7 loop, forming a convex surface within the hAGO1 nucleic-acid-binding channel near the inactive catalytic site. We predicted that even upon restoration of the catalytic tetrad, hAGO1-cS7 sterically hinders the placement of a fully paired guide-target RNA duplex into the endonuclease active site. Consistent with this hypothesis, reconstitution of the catalytic tetrad with R805H led to low-level hAGO1 cleavage activity, whereas combining R805H with cS7 substitutions P670S and P675Q substantially augmented hAGO1 activity. Evolutionary amino acid changes to hAGO1 were readily reversible, suggesting that loading of guide RNA and pairing of seed-based miRNA and target RNA constrain its sequence drift.
Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity.,Nakanishi K, Ascano M, Gogakos T, Ishibe-Murakami S, Serganov AA, Briskin D, Morozov P, Tuschl T, Patel DJ Cell Rep. 2013 Jun 27;3(6):1893-900. doi: 10.1016/j.celrep.2013.06.010. PMID:23809764[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
- ↑ Nakanishi K, Ascano M, Gogakos T, Ishibe-Murakami S, Serganov AA, Briskin D, Morozov P, Tuschl T, Patel DJ. Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity. Cell Rep. 2013 Jun 27;3(6):1893-900. doi: 10.1016/j.celrep.2013.06.010. PMID:23809764 doi:10.1016/j.celrep.2013.06.010
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