3le4
From Proteopedia
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==Crystal structure of the DGCR8 dimerization domain== | ==Crystal structure of the DGCR8 dimerization domain== | ||
| - | <StructureSection load='3le4' size='340' side='right' caption='[[3le4]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='3le4' size='340' side='right'caption='[[3le4]], [[Resolution|resolution]] 1.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3le4]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3le4]] is a 1 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=3LE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LE4 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.701Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3le4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3le4 OCA], [https://pdbe.org/3le4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3le4 RCSB], [https://www.ebi.ac.uk/pdbsum/3le4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3le4 ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/DGCR8_HUMAN DGCR8_HUMAN] Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Involved in the silencing of embryonic stem cells self-renewal.<ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:16963499</ref> <ref>PMID:17159994</ref> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/le/3le4_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/le/3le4_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</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=3le4 ConSurf]. | </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=3le4 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Maturation of microRNAs (miRNAs, approximately 22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 A resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis. | ||
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| - | Structure of the dimerization domain of DiGeorge critical region 8.,Senturia R, Faller M, Yin S, Loo JA, Cascio D, Sawaya MR, Hwang D, Clubb RT, Guo F Protein Sci. 2010 Jul;19(7):1354-65. PMID:20506313<ref>PMID:20506313</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 3le4" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Cascio | + | [[Category: Large Structures]] |
| - | [[Category: Guo | + | [[Category: Cascio D]] |
| - | [[Category: Sawaya | + | [[Category: Guo F]] |
| - | [[Category: Senturia | + | [[Category: Sawaya M]] |
| - | + | [[Category: Senturia R]] | |
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Current revision
Crystal structure of the DGCR8 dimerization domain
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