View source for 5zak


==Cryo-EM structure of human Dicer and its complexes with a pre-miRNA substrate==
<SX load='5zak' size='340' side='right' viewer='molstar' caption='[[5zak]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5zak]] 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=5ZAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZAK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4&#8491;</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=5zak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zak OCA], [https://pdbe.org/5zak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zak RCSB], [https://www.ebi.ac.uk/pdbsum/5zak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zak ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/TRBP2_HUMAN TRBP2_HUMAN] Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto EIF2C2/AGO2. EIF2C2/AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1. Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1, and stimulates translation of TAR-containing RNAs. This is achieved in part at least by binding to and inhibiting EIF2AK2/PKR, thereby reducing phosphorylation and inhibition of EIF2S1/eIF-2-alpha. May also promote translation of TAR-containing RNAs independently of EIF2AK2/PKR.<ref>PMID:12475984</ref> <ref>PMID:16271387</ref> <ref>PMID:16142218</ref> <ref>PMID:16357216</ref> <ref>PMID:15973356</ref> <ref>PMID:16424907</ref> <ref>PMID:17452327</ref> <ref>PMID:18178619</ref> <ref>PMID:19219043</ref> 
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== Publication Abstract from PubMed ==
Human Dicer (hDicer) is a multi-domain protein belonging to the RNase III family. It plays pivotal roles in small RNA biogenesis during the RNA interference (RNAi) pathway by processing a diverse range of double-stranded RNA (dsRNA) precursors to generate approximately 22 nt microRNA (miRNA) or small interfering RNA (siRNA) products for sequence-directed gene silencing. In this work, we solved the cryoelectron microscopy (cryo-EM) structure of hDicer in complex with its cofactor protein TRBP and revealed the precise spatial arrangement of hDicer's multiple domains. We further solved structures of the hDicer-TRBP complex bound with pre-let-7 RNA in two distinct conformations. In combination with biochemical analysis, these structures reveal a property of the hDicer-TRBP complex to promote the stability of pre-miRNA's stem duplex in a pre-dicing state. These results provide insights into the mechanism of RNA processing by hDicer and illustrate the regulatory role of hDicer's N-terminal helicase domain.

Cryo-EM Structure of Human Dicer and Its Complexes with a Pre-miRNA Substrate.,Liu Z, Wang J, Cheng H, Ke X, Sun L, Zhang QC, Wang HW Cell. 2018 May 17;173(5):1191-1203.e12. doi: 10.1016/j.cell.2018.03.080. Epub, 2018 Apr 26. PMID:29706542<ref>PMID:29706542</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5zak" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
== References ==
<references/>
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cheng H]]
[[Category: Ke X]]
[[Category: Liu Z]]
[[Category: Sun L]]
[[Category: Wang H-W]]
[[Category: Wang J]]
[[Category: Zhang QC]]