5b16

From Proteopedia

(Difference between revisions)

Current revision

X-ray structure of DROSHA in complex with the C-terminal tail of DGCR8.

Structural highlights

5b16 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Publication Abstract from PubMed

MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing. VIDEO ABSTRACT.

Structure of Human DROSHA.,Kwon SC, Nguyen TA, Choi YG, Jo MH, Hohng S, Kim VN, Woo JS Cell. 2016 Jan 14;164(1-2):81-90. doi: 10.1016/j.cell.2015.12.019. Epub 2015 Dec , 31. PMID:26748718^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wu H, Xu H, Miraglia LJ, Crooke ST. Human RNase III is a 160-kDa protein involved in preribosomal RNA processing. J Biol Chem. 2000 Nov 24;275(47):36957-65. PMID:10948199 doi:http://dx.doi.org/10.1074/jbc.M005494200
↑ Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003 Sep 25;425(6956):415-9. PMID:14508493 doi:http://dx.doi.org/10.1038/nature01957
↑ Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004 Dec 14;14(23):2162-7. PMID:15589161 doi:10.1016/j.cub.2004.11.001
↑ Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004 Dec 15;18(24):3016-27. Epub 2004 Dec 1. PMID:15574589 doi:10.1101/gad.1262504
↑ Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004 Nov 11;432(7014):235-40. Epub 2004 Nov 7. PMID:15531877 doi:10.1038/nature03120
↑ Zeng Y, Yi R, Cullen BR. Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 2005 Jan 12;24(1):138-48. Epub 2004 Nov 25. PMID:15565168 doi:http://dx.doi.org/10.1038/sj.emboj.7600491
↑ Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006 Jun 2;125(5):887-901. PMID:16751099 doi:10.1016/j.cell.2006.03.043
↑ Pauley KM, Eystathioy T, Jakymiw A, Hamel JC, Fritzler MJ, Chan EK. Formation of GW bodies is a consequence of microRNA genesis. EMBO Rep. 2006 Sep;7(9):904-10. Epub 2006 Aug 11. PMID:16906129 doi:7400783
↑ Faller M, Matsunaga M, Yin S, Loo JA, Guo F. Heme is involved in microRNA processing. Nat Struct Mol Biol. 2007 Jan;14(1):23-9. Epub 2006 Dec 10. PMID:17159994 doi:10.1038/nsmb1182
↑ Kwon SC, Nguyen TA, Choi YG, Jo MH, Hohng S, Kim VN, Woo JS. Structure of Human DROSHA. Cell. 2016 Jan 14;164(1-2):81-90. doi: 10.1016/j.cell.2015.12.019. Epub 2015 Dec , 31. PMID:26748718 doi:http://dx.doi.org/10.1016/j.cell.2015.12.019

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b16"

@@ Line 3: / Line 3: @@
 <StructureSection load='5b16' size='340' side='right'caption='[[5b16]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5b16]] is a 3 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=5B16 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B16 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5b16]] is a 3 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=5B16 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5B16 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5b16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b16 OCA], [https://pdbe.org/5b16 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5b16 RCSB], [https://www.ebi.ac.uk/pdbsum/5b16 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5b16 ProSAT]</span></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5b16 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b16 OCA], [http://pdbe.org/5b16 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b16 RCSB], [http://www.ebi.ac.uk/pdbsum/5b16 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b16 ProSAT]</span></td></tr>
 </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>
+[https://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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ribonuclease III]]
+[[Category: Choi YG]]
-[[Category: Choi, Y G]]
+[[Category: Hohng S]]
-[[Category: Hohng, S]]
+[[Category: Jo MH]]
-[[Category: Jo, M H]]
+[[Category: Kim VN]]
-[[Category: Kim, V N]]
+[[Category: Kwon SC]]
-[[Category: Kwon, S C]]
+[[Category: Nguyen TA]]
-[[Category: Nguyen, T A]]
+[[Category: Woo JS]]
-[[Category: Woo, J S]]
-[[Category: Endonuclease]]
-[[Category: Hydrolase]]
-[[Category: Rnase iii]]
-[[Category: Trimeric complex]]
-[[Category: Zinc finger]]

5b16

From Proteopedia

Current revision

X-ray structure of DROSHA in complex with the C-terminal tail of DGCR8.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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