6cbd

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<StructureSection load='6cbd' size='340' side='right'caption='[[6cbd]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='6cbd' size='340' side='right'caption='[[6cbd]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6cbd]] is a 3 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=6CBD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CBD FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6cbd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CBD FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.203&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AGO2, EIF2C2 ([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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TRP:TRYPTOPHAN'>TRP</scene></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=6cbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cbd OCA], [http://pdbe.org/6cbd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cbd RCSB], [http://www.ebi.ac.uk/pdbsum/6cbd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cbd ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6cbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cbd OCA], [https://pdbe.org/6cbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cbd RCSB], [https://www.ebi.ac.uk/pdbsum/6cbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cbd ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/AGO2_HUMAN AGO2_HUMAN]] Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include EIF2C2/AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by EIF2C2/AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions.<ref>PMID:15105377</ref> <ref>PMID:15260970</ref> <ref>PMID:15337849</ref> <ref>PMID:15284456</ref> <ref>PMID:16271387</ref> <ref>PMID:16289642</ref> <ref>PMID:16142218</ref> <ref>PMID:16357216</ref> <ref>PMID:15800637</ref> <ref>PMID:16081698</ref> <ref>PMID:16936728</ref> <ref>PMID:16756390</ref> <ref>PMID:17382880</ref> <ref>PMID:17524464</ref> <ref>PMID:17932509</ref> <ref>PMID:17531811</ref> <ref>PMID:17507929</ref> <ref>PMID:18048652</ref> <ref>PMID:18771919</ref> <ref>PMID:18690212</ref> <ref>PMID:18178619</ref> <ref>PMID:19167051</ref>
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[https://www.uniprot.org/uniprot/AGO2_HUMAN AGO2_HUMAN] Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include EIF2C2/AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by EIF2C2/AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions.<ref>PMID:15105377</ref> <ref>PMID:15260970</ref> <ref>PMID:15337849</ref> <ref>PMID:15284456</ref> <ref>PMID:16271387</ref> <ref>PMID:16289642</ref> <ref>PMID:16142218</ref> <ref>PMID:16357216</ref> <ref>PMID:15800637</ref> <ref>PMID:16081698</ref> <ref>PMID:16936728</ref> <ref>PMID:16756390</ref> <ref>PMID:17382880</ref> <ref>PMID:17524464</ref> <ref>PMID:17932509</ref> <ref>PMID:17531811</ref> <ref>PMID:17507929</ref> <ref>PMID:18048652</ref> <ref>PMID:18771919</ref> <ref>PMID:18690212</ref> <ref>PMID:18178619</ref> <ref>PMID:19167051</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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miRISC is a multi-protein assembly that uses microRNAs (miRNAs) to identify mRNAs targeted for repression. Dozens of miRISC-associated proteins have been identified, and interactions between many factors have been examined in detail. However, the physical nature of the complex remains unknown. Here, we show that two core protein components of human miRISC, Argonaute2 (Ago2) and TNRC6B, condense into phase-separated droplets in vitro and in live cells. Phase separation is promoted by multivalent interactions between the glycine/tryptophan (GW)-rich domain of TNRC6B and three evenly spaced tryptophan-binding pockets in the Ago2 PIWI domain. miRISC droplets formed in vitro recruit deadenylation factors and sequester target RNAs from the bulk solution. The condensation of miRISC is accompanied by accelerated deadenylation of target RNAs bound to Ago2. The combined results may explain how miRISC silences mRNAs of varying size and structure and provide experimental evidence that protein-mediated phase separation can facilitate an RNA processing reaction.
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Phase Transitions in the Assembly and Function of Human miRISC.,Sheu-Gruttadauria J, MacRae IJ Cell. 2018 Mar 16. pii: S0092-8674(18)30228-9. doi: 10.1016/j.cell.2018.02.051. PMID:29576456<ref>PMID:29576456</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6cbd" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: MacRae, I J]]
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[[Category: Unidentified]]
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[[Category: Sheu-Gruttadauria, J]]
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[[Category: MacRae IJ]]
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[[Category: Gw182]]
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[[Category: Sheu-Gruttadauria J]]
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[[Category: Microrna]]
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[[Category: Mirisc]]
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[[Category: Mirna]]
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[[Category: Rna binding protein]]
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Current revision

Crystal Structure of Human Argonaute2 Bound to Three Tryptophans

PDB ID 6cbd

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