4h4a

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Crystal structure of the C-terminal domain of Drosophila melanogaster ZucchiniCrystal structure of the C-terminal domain of Drosophila melanogaster Zucchini

Structural highlights

4h4a 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.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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) are a gonad-specific class of small RNAs that associate with the Piwi clade of Argonaute proteins and play a key role in transposon silencing in animals. Since biogenesis of piRNAs is independent of the double-stranded RNA-processing enzyme Dicer, an alternative nuclease that can process single-stranded RNA transcripts has been long sought. A Phospholipase D-like protein, Zucchini, that is essential for piRNA processing has been proposed to be a nuclease acting in piRNA biogenesis. Here we describe the crystal structure of Zucchini from Drosophila melanogaster and show that it is very similar to the bacterial endonuclease, Nuc. The structure also reveals that homodimerization induces major conformational changes assembling the active site. The active site is situated on the dimer interface at the bottom of a narrow groove that can likely accommodate single-stranded nucleic acid substrates. Furthermore, biophysical analysis identifies protein segments essential for dimerization and provides insights into regulation of Zucchini's activity.

Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc.,Voigt F, Reuter M, Kasaruho A, Schulz EC, Pillai RS, Barabas O RNA. 2012 Oct 19. PMID:23086923[8]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ Voigt F, Reuter M, Kasaruho A, Schulz EC, Pillai RS, Barabas O. Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc. RNA. 2012 Oct 19. PMID:23086923 doi:http://dx.doi.org/10.1261/rna.034967.112

4h4a, resolution 2.20Å

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