View source for 4ngd


==Structure of human Dicer Platform-PAZ-Connector Helix cassette in complex with 12-mer siRNA having 5'-p and UU-3' ends (1.95 Angstrom resolution)==
<StructureSection load='4ngd' size='340' side='right' caption='[[4ngd]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ngd]] is a 2 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=4NGD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NGD FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ngb|4ngb]], [[4ngc|4ngc]], [[4ngf|4ngf]], [[4ngg|4ngg]], [[4nh3|4nh3]], [[4nh5|4nh5]], [[4nh6|4nh6]], [[4nha|4nha]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DICER, DICER1, HERNA, KIAA0928 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ngd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ngd OCA], [http://pdbe.org/4ngd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ngd RCSB], [http://www.ebi.ac.uk/pdbsum/4ngd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ngd ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/DICER_HUMAN DICER_HUMAN]] Defects in DICER1 are a cause of pleuropulmonary blastoma (PPB) [MIM:[http://omim.org/entry/601200 601200]]. PPB is a rare pediatric tumor of the lung that arises during fetal lung development and is often part of an inherited cancer syndrome. PPBs contain both epithelial and mesenchymal cells. Early in tumorigenesis, cysts form in lung airspaces, and these cysts are lined with benign-appearing epithelium. Mesenchymal cells susceptible to malignant transformation reside within the cyst walls and form a dense 'cambium' layer beneath the epithelial lining. In a subset of patients, overgrowth of the mesenchymal cells produces a sarcoma, a transition that is associated with a poorer prognosis.<ref>PMID:21882293</ref> <ref>PMID:19556464</ref>   Defects in DICER1 are the cause of goiter multinodular type 1 with or without Sertoli-Leydig cell tumors (MNG1) [MIM:[http://omim.org/entry/138800 138800]]. A common disorder characterized by nodular overgrowth of the thyroid gland. Some individuals may also develop Sertoli-Leydig cell tumors, usually of the ovary.<ref>PMID:21882293</ref> <ref>PMID:21205968</ref>   Note=DICER1 mutations have been found in uterine cervix embryonal rhabdomyosarcoma, primitive neuroectodermal tumor, Wilms tumor, pulmonary sequestration and juvenile intestinal polyp (PubMed:21882293). Somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in non-epithelial ovarian tumors. These mutations do not abolish DICER1 function but alter it in specific cell types, a novel mechanism through which perturbation of microRNA processing may be oncogenic (PubMed:22187960).<ref>PMID:21882293</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/DICER_HUMAN DICER_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. Also cleaves double-stranded RNA to produce short interfering RNAs (siRNAs) which target the selective destruction of complementary RNAs.<ref>PMID:15242644</ref> <ref>PMID:16271387</ref> <ref>PMID:16289642</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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have solved two families of crystal structures of the human Dicer "platform-PAZ-connector helix" cassette in complex with small interfering RNAs (siRNAs). The structures possess two adjacently positioned pockets: a 2 nt 3'-overhang-binding pocket within the PAZ domain (3' pocket) and a phosphate-binding pocket within the platform domain (phosphate pocket). One family of complexes contains a knob-like alpha-helical protrusion, designated "hDicer-specific helix," that separates the two pockets and orients the bound siRNA away from the surface of Dicer, which could be indicative of a product release/transfer state. In the second complex, the helical protrusion is melted/disordered and the bound siRNA is aligned toward the surface of Dicer, suggestive of a cleavage-competent state. These structures allow us to propose that the transition from the cleavage-competent to the postulated product release/transfer state may involve release of the 5'-phosphate from the phosphate pocket while retaining the 3' overhang in the 3' pocket.

A Phosphate-Binding Pocket within the Platform-PAZ-Connector Helix Cassette of Human Dicer.,Tian Y, Simanshu DK, Ma JB, Park JE, Heo I, Kim VN, Patel DJ Mol Cell. 2014 Feb 20;53(4):606-16. doi: 10.1016/j.molcel.2014.01.003. Epub 2014 , Jan 30. PMID:24486018<ref>PMID:24486018</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ngd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ribonuclease|Ribonuclease]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Patel, D J]]
[[Category: Simanshu, D K]]
[[Category: Tian, Y]]
[[Category: Connector helix]]
[[Category: Endoribonuclease]]
[[Category: Hydrolase-rna complex]]
[[Category: Paz domain]]
[[Category: Platform domain]]
[[Category: Pre-mirna]]
[[Category: Rnase iii domain]]
[[Category: Sirna]]