View source for 3c4t


==Structure of RNaseIIIb and dsRNA binding domains of mouse Dicer==
<StructureSection load='3c4t' size='340' side='right'caption='[[3c4t]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3c4t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C4T FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</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;'>[[3c4b|3c4b]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dicer1, Dicer, Mdcr ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3c4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c4t OCA], [https://pdbe.org/3c4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c4t RCSB], [https://www.ebi.ac.uk/pdbsum/3c4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c4t ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/DICER_MOUSE DICER_MOUSE]] 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. Also cleaves double-stranded RNA to produce short interfering RNAs (siRNAs) which target the selective destruction of complementary RNAs (By similarity).  Involved in cleaving double-stranded RNA in the RNA interference (RNAi) pathway. It produces 21 to 23 bp dsRNAs (siRNAs) which target the selective destruction of homologous RNAs. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c4/3c4t_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3c4t ConSurf].
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== Publication Abstract from PubMed ==
Dicer, an RNase III enzyme, initiates RNA interference by processing precursor dsRNAs into mature microRNAs and small-interfering RNAs. It is also involved in loading and activation of the RNA-induced silencing complex. Here, we report the crystal structures of a catalytically active fragment of mouse Dicer, containing the RNase IIIb and dsRNA binding domains, in its apo and Cd(2+)-bound forms, at 1.68- and 2.8-A resolution, respectively. Models of this structure with dsRNA reveal that a lysine residue, highly conserved in Dicer RNase IIIa and IIIb domains and in Drosha RNase IIIb domains, has the potential to participate in the phosphodiester bond cleavage reaction by stabilizing the transition state and leaving group of the scissile bond. Mutational and enzymatic assays confirm the importance of this lysine in dsRNA cleavage, suggesting that this lysine represents a conserved catalytic residue of Dicers. The structures also reveals a approximately 45-aa region within the RNase IIIb domain that harbors an alpha-helix at the N-terminal half and a flexible loop at the C-terminal half, features not present in previously reported structures of homologous RNase III domains from either bacterial RNase III enzymes or Giardia Dicer. N-terminal residues of this alpha-helix have the potential to engage in minor groove interaction with dsRNA substrates.

Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage.,Du Z, Lee JK, Tjhen R, Stroud RM, James TL Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2391-6. Epub 2008 Feb 11. PMID:18268334<ref>PMID:18268334</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 3c4t" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribonuclease 3D structures|Ribonuclease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Du, Z]]
[[Category: James, T L]]
[[Category: Lee, J K]]
[[Category: Stroud, R M]]
[[Category: Tjhen, R J]]
[[Category: Atp-binding]]
[[Category: Endonuclease]]
[[Category: Helicase]]
[[Category: Hydrolase]]
[[Category: Nuclease]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Rna-binding]]
[[Category: Rna-mediated gene silencing]]
[[Category: Rnase]]