View source for 3qx9


==Crystal structure of MID domain from hAGO2 in complex with ATP==
<StructureSection load='3qx9' size='340' side='right'caption='[[3qx9]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3qx9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QX9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3luc|3luc]], [[3qx8|3qx8]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2C2, AGO2 ([https://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=3qx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qx9 OCA], [https://pdbe.org/3qx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qx9 RCSB], [https://www.ebi.ac.uk/pdbsum/3qx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qx9 ProSAT]</span></td></tr>
</table>
== Function ==
[[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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In RNA silencing, microRNA (miRNA)-mediated translational repression occurs through mechanisms that do not invoke messenger-RNA (mRNA) target cleavage by Argonaute proteins. The nature of these mechanisms is unclear, but several recent studies have proposed that a direct interaction between the mRNA-cap and the middle (MID) domain of Argonautes is involved. Here, we present crystallographic and NMR data demonstrating that cap analogues do not bind significantly to the isolated MID domain of human Argonaute 2 (hAGO2) and are found in the miRNA 5'-nucleotide binding site in an implausible binding mode. Additionally, in vitro pull-down experiments with full-length hAGO2 indicate that the interaction with cap analogues is nonspecific.

Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain.,Frank F, Fabian MR, Stepinski J, Jemielity J, Darzynkiewicz E, Sonenberg N, Nagar B EMBO Rep. 2011 Apr 8. PMID:21475248<ref>PMID:21475248</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qx9" 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/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Darzynkiewicz, E]]
[[Category: Fabian, M R]]
[[Category: Frank, F]]
[[Category: Jemielity, J]]
[[Category: Nagar, B]]
[[Category: Sonenberg, N]]
[[Category: Stepinski, J]]
[[Category: Rna binding protein]]
[[Category: Rossmann-like fold]]