4gen

From Proteopedia

(Difference between revisions)

Revision as of 09:20, 25 December 2014

Crystal structure of Zucchini (monomer)

Structural highlights

4gen is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	4gel, 4gem
Gene:	zuc, CG12314 (Drosophila melanogaster)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[ZUC_DROME] Cardiolipin hydrolase present at the mitochondrial outer membrane required for piRNA metabolic process. Acts by catalyzing the hydrolysis of cardiolipin (diphosphatidylglycerol) to form phosphatidate (phosphatidic acid or PA) at the mitochondrial outer membrane surface, promoting the piRNA metabolic process. Plays a key role in primary biogenesis of piRNAs and is required during oogenesis to repress transposable elements and prevent their mobilization. piRNAs mediate the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Involved in trans-silencing effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin via its role in piRNA biogenesis.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines. piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery. Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway. Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member, is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75 A resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD) showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5'-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.

Structure and function of Zucchini endoribonuclease in piRNA biogenesis.,Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O Nature. 2012 Nov 8;491(7423):284-7. doi: 10.1038/nature11509. Epub 2012 Oct 14. PMID:23064230^[8]

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

References

↑ Pane A, Wehr K, Schupbach T. zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell. 2007 Jun;12(6):851-62. PMID:17543859 doi:10.1016/j.devcel.2007.03.022
↑ Saito K, Inagaki S, Mituyama T, Kawamura Y, Ono Y, Sakota E, Kotani H, Asai K, Siomi H, Siomi MC. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila. Nature. 2009 Oct 29;461(7268):1296-9. doi: 10.1038/nature08501. Epub 2009 Oct 7. PMID:19812547 doi:10.1038/nature08501
↑ Olivieri D, Sykora MM, Sachidanandam R, Mechtler K, Brennecke J. An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila. EMBO J. 2010 Oct 6;29(19):3301-17. doi: 10.1038/emboj.2010.212. Epub 2010 Sep 3. PMID:20818334 doi:10.1038/emboj.2010.212
↑ Saito K, Ishizu H, Komai M, Kotani H, Kawamura Y, Nishida KM, Siomi H, Siomi MC. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila. Genes Dev. 2010 Nov 15;24(22):2493-8. doi: 10.1101/gad.1989510. Epub 2010 Oct 21. PMID:20966047 doi:10.1101/gad.1989510
↑ Haase AD, Fenoglio S, Muerdter F, Guzzardo PM, Czech B, Pappin DJ, Chen C, Gordon A, Hannon GJ. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila. Genes Dev. 2010 Nov 15;24(22):2499-504. doi: 10.1101/gad.1968110. Epub 2010 Oct, 21. PMID:20966049 doi:10.1101/gad.1968110
↑ Todeschini AL, Teysset L, Delmarre V, Ronsseray S. The epigenetic trans-silencing effect in Drosophila involves maternally-transmitted small RNAs whose production depends on the piRNA pathway and HP1. PLoS One. 2010 Jun 14;5(6):e11032. doi: 10.1371/journal.pone.0011032. PMID:20559422 doi:10.1371/journal.pone.0011032
↑ Huang H, Gao Q, Peng X, Choi SY, Sarma K, Ren H, Morris AJ, Frohman MA. piRNA-associated germline nuage formation and spermatogenesis require MitoPLD profusogenic mitochondrial-surface lipid signaling. Dev Cell. 2011 Mar 15;20(3):376-87. doi: 10.1016/j.devcel.2011.01.004. PMID:21397848 doi:10.1016/j.devcel.2011.01.004
↑ Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O. Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature. 2012 Nov 8;491(7423):284-7. doi: 10.1038/nature11509. Epub 2012 Oct 14. PMID:23064230 doi:http://dx.doi.org/10.1038/nature11509

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/4gen"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4gen|  PDB=4gen  |  SCENE=  }}
+==Crystal structure of Zucchini (monomer)==
-===Crystal structure of Zucchini (monomer)===
+<StructureSection load='4gen' size='340' side='right' caption='[[4gen]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23064230}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4gen]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GEN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GEN FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4gel|4gel]], [[4gem|4gem]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">zuc, CG12314 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 Drosophila melanogaster])</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=4gen FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gen OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gen RCSB], [http://www.ebi.ac.uk/pdbsum/4gen PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ZUC_DROME ZUC_DROME]] Cardiolipin hydrolase present at the mitochondrial outer membrane required for piRNA metabolic process. Acts by catalyzing the hydrolysis of cardiolipin (diphosphatidylglycerol) to form phosphatidate (phosphatidic acid or PA) at the mitochondrial outer membrane surface, promoting the piRNA metabolic process. Plays a key role in primary biogenesis of piRNAs and is required during oogenesis to repress transposable elements and prevent their mobilization. piRNAs mediate the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Involved in trans-silencing effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin via its role in piRNA biogenesis.<ref>PMID:17543859</ref> <ref>PMID:19812547</ref> <ref>PMID:20818334</ref> <ref>PMID:20966047</ref> <ref>PMID:20966049</ref> <ref>PMID:20559422</ref> <ref>PMID:21397848</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines. piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery. Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway. Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member, is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75 A resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD) showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5'-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.
-==Function==
+Structure and function of Zucchini endoribonuclease in piRNA biogenesis.,Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani MK, Bonnefond L, Matsumoto N, Nishizawa T, Nakanaga K, Aoki J, Ishitani R, Siomi H, Siomi MC, Nureki O Nature. 2012 Nov 8;491(7423):284-7. doi: 10.1038/nature11509. Epub 2012 Oct 14. PMID:23064230<ref>PMID:23064230</ref>
-[[http://www.uniprot.org/uniprot/ZUC_DROME ZUC_DROME]] Cardiolipin hydrolase present at the mitochondrial outer membrane required for piRNA metabolic process. Acts by catalyzing the hydrolysis of cardiolipin (diphosphatidylglycerol) to form phosphatidate (phosphatidic acid or PA) at the mitochondrial outer membrane surface, promoting the piRNA metabolic process. Plays a key role in primary biogenesis of piRNAs and is required during oogenesis to repress transposable elements and prevent their mobilization. piRNAs mediate the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Involved in trans-silencing effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin via its role in piRNA biogenesis.<ref>PMID:17543859</ref><ref>PMID:19812547</ref><ref>PMID:20818334</ref><ref>PMID:20966047</ref><ref>PMID:20966049</ref><ref>PMID:20559422</ref><ref>PMID:21397848</ref>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4gen]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GEN OCA].
+</div>
+== References ==
-==Reference==
+<references/>
-<references group="xtra"/><references/>
+__TOC__
+</StructureSection>
 [[Category: Drosophila melanogaster]]
-[[Category: Fukuhara, S.]]
+[[Category: Fukuhara, S]]
-[[Category: Ishitani, R.]]
+[[Category: Ishitani, R]]
-[[Category: Nishimasu, H.]]
+[[Category: Nishimasu, H]]
-[[Category: Nureki, O.]]
+[[Category: Nureki, O]]
 [[Category: Hydrolase]]
 [[Category: Nuclease]]
 [[Category: Phospholipase d]]
 [[Category: Pirna]]

4gen

From Proteopedia

Revision as of 09:20, 25 December 2014

Crystal structure of Zucchini (monomer)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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