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6lxd
From Proteopedia
(Difference between revisions)
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==Pri-miRNA bound DROSHA-DGCR8 complex== | ==Pri-miRNA bound DROSHA-DGCR8 complex== | ||
| - | <StructureSection load='6lxd' size='340' side='right'caption='[[6lxd]]' scene=''> | + | <StructureSection load='6lxd' size='340' side='right'caption='[[6lxd]], [[Resolution|resolution]] 3.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LXD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LXD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6lxd]] is a 4 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=6LXD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6LXD FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lxd OCA], [http://pdbe.org/6lxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lxd RCSB], [http://www.ebi.ac.uk/pdbsum/6lxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lxd ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DROSHA, RN3, RNASE3L, RNASEN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DGCR8, C22orf12, DGCRK6, LP4941 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribonuclease_III Ribonuclease III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.3 3.1.26.3] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lxd OCA], [http://pdbe.org/6lxd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lxd RCSB], [http://www.ebi.ac.uk/pdbsum/6lxd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lxd ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/RNC_HUMAN RNC_HUMAN]] Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease 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, DROSHA cleaves the 3' and 5' strands of a stem-loop in pri-miRNAs (processing center 11 bp from the dsRNA-ssRNA junction) to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. Involved also in pre-rRNA processing. Cleaves double-strand RNA and does not cleave single-strand RNA. Involved in the formation of GW bodies.<ref>PMID:10948199</ref> <ref>PMID:14508493</ref> <ref>PMID:15589161</ref> <ref>PMID:15574589</ref> <ref>PMID:15531877</ref> <ref>PMID:15565168</ref> <ref>PMID:16751099</ref> <ref>PMID:16906129</ref> <ref>PMID:17159994</ref> [[http://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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A commencing and critical step in miRNA biogenesis involves processing of pri-miRNAs in the nucleus by Microprocessor. An important, but not completely understood, question is how Drosha, the catalytic subunit of Microprocessor, binds pri-miRNAs and correctly specifies cleavage sites. Here we report the cryoelectron microscopy structures of the Drosha-DGCR8 complex with and without a pri-miRNA. The RNA-bound structure provides direct visualization of the tertiary structure of pri-miRNA and shows that a helix hairpin in the extended PAZ domain and the mobile basic (MB) helix in the RNase IIIa domain of Drosha coordinate to recognize the single-stranded to double-stranded junction of RNA, whereas the dsRNA binding domain makes extensive contacts with the RNA stem. Furthermore, the RNA-free structure reveals an autoinhibitory conformation of the PAZ helix hairpin. These findings provide mechanistic insights into pri-miRNA cleavage site selection and conformational dynamics governing pri-miRNA recognition by the catalytic component of Microprocessor. | ||
| + | |||
| + | Structural Basis for pri-miRNA Recognition by Drosha.,Jin W, Wang J, Liu CP, Wang HW, Xu RM Mol Cell. 2020 Mar 25. pii: S1097-2765(20)30144-1. doi:, 10.1016/j.molcel.2020.02.024. PMID:32220645<ref>PMID:32220645</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6lxd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Jin W]] | + | [[Category: Ribonuclease III]] |
| - | [[Category: Liu | + | [[Category: Jin, W]] |
| - | [[Category: Wang | + | [[Category: Liu, C P]] |
| - | [[Category: Wang J]] | + | [[Category: Wang, H W]] |
| - | [[Category: Xu | + | [[Category: Wang, J]] |
| + | [[Category: Xu, R M]] | ||
| + | [[Category: Hydrolase-rna binding protein-rna complex]] | ||
| + | [[Category: Ribonuclease]] | ||
| + | [[Category: Rna binding protein]] | ||
Revision as of 07:16, 27 May 2020
Pri-miRNA bound DROSHA-DGCR8 complex
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