6kr6

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Crystal structure of Drosophila PiwiCrystal structure of Drosophila Piwi

Structural highlights

6kr6 is a 2 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 2.9Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PIWI_DROME Acts via the piwi-interacting RNA (piRNA) metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons (PubMed:26808625, PubMed:15817569, PubMed:17346786). Directly binds piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements (PubMed:16882972). In ovarian somatic cells, mediates silencing of transposable elements at the transcriptional level in a mael-dependent manner (PubMed:23159368, PubMed:28472469). Involved in silencing of long terminal repeat (LTR) retrotransposons in male germline (PubMed:15817569). In testis, regulates spermatogenesis together with Tudor-SN (PubMed:26808625). In germ cells, mediates silencing at both transcriptional and post-transcriptional levels and is involved in the maintenance of populations of primary and secondary piRNAs. Piwi-mediated transcriptional silencing is accompanied by the formation of His3 'Lys-9' trimethylated (H3K9me3) euchromatin and heterochromatin (PubMed:23434410, PubMed:23392610). In ovary, associates predominantly with antisense piRNAs that contain uridine at their 5' end. Association with sense piRNAs is also observed but to a lesser extent. Mediates a somatic signaling mechanism required for the maintenance of germline stem cells to produce and maintain a daughter germline stem cell (PubMed:9851978, PubMed:10631171, PubMed:9199372, PubMed:16949822). It is not essential for the further differentiation of the committed daughter cell (PubMed:9851978). Acts cell autonomously to promote germline stem cell division (PubMed:9851978, PubMed:10631171). Its role in stem cell maintenance does not seem to require nuclear localization. Required maternally for the posterior localization of osk and vas and for pole cell formation during oogenesis and early embryogenesis (PubMed:16949822). Together with Hop and Hsp83, mediates canalization, also known as developmental robustness, likely via epigenetic silencing of existing genetic variants and suppression of transposon-induced new genetic variation (PubMed:21186352). Shows RNA cleavage activity, although is not required for any of its known functions (PubMed:9199372, PubMed:16882972, PubMed:23297219).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]

Publication Abstract from PubMed

PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs), and silence transposons in animal gonads. Here, we report the crystal structure of the Drosophila PIWI-clade Argonaute Piwi in complex with endogenous piRNAs, at 2.9 A resolution. A structural comparison of Piwi with other Argonautes highlights the PIWI-specific structural features, such as the overall domain arrangement and metal-dependent piRNA recognition. Our structural and biochemical data reveal that, unlike other Argonautes including silkworm Siwi, Piwi has a non-canonical DVDK tetrad and lacks the RNA-guided RNA cleaving slicer activity. Furthermore, we find that the Piwi mutant with the canonical DEDH catalytic tetrad exhibits the slicer activity and readily dissociates from less complementary RNA targets after the slicer-mediated cleavage, suggesting that the slicer activity could compromise the Piwi-mediated co-transcriptional silencing. We thus propose that Piwi lost the slicer activity during evolution to serve as an RNA-guided RNA-binding platform, thereby ensuring faithful co-transcriptional silencing of transposons.

Crystal structure of Drosophila Piwi.,Yamaguchi S, Oe A, Nishida KM, Yamashita K, Kajiya A, Hirano S, Matsumoto N, Dohmae N, Ishitani R, Saito K, Siomi H, Nishimasu H, Siomi MC, Nureki O Nat Commun. 2020 Feb 12;11(1):858. doi: 10.1038/s41467-020-14687-1. PMID:32051406[20]

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

References

  1. ↑ Cox DN, Chao A, Lin H. piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. Development. 2000 Feb;127(3):503-14. PMID:10631171
  2. ↑ Kalmykova AI, Klenov MS, Gvozdev VA. Argonaute protein PIWI controls mobilization of retrotransposons in the Drosophila male germline. Nucleic Acids Res. 2005 Apr 7;33(6):2052-9. doi: 10.1093/nar/gki323. Print 2005. PMID:15817569 doi:http://dx.doi.org/10.1093/nar/gki323
  3. ↑ Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes Dev. 2006 Aug 15;20(16):2214-22. doi: 10.1101/gad.1454806. Epub 2006 Aug 1. PMID:16882972 doi:http://dx.doi.org/10.1101/gad.1454806
  4. ↑ Megosh HB, Cox DN, Campbell C, Lin H. The role of PIWI and the miRNA machinery in Drosophila germline determination. Curr Biol. 2006 Oct 10;16(19):1884-94. doi: 10.1016/j.cub.2006.08.051. Epub 2006 , Aug 31. PMID:16949822 doi:http://dx.doi.org/10.1016/j.cub.2006.08.051
  5. ↑ Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, Hannon GJ. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 2007 Mar 23;128(6):1089-103. doi: 10.1016/j.cell.2007.01.043. Epub 2007 Mar, 8. PMID:17346786 doi:http://dx.doi.org/10.1016/j.cell.2007.01.043
  6. ↑ Brower-Toland B, Findley SD, Jiang L, Liu L, Yin H, Dus M, Zhou P, Elgin SC, Lin H. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes Dev. 2007 Sep 15;21(18):2300-11. doi: 10.1101/gad.1564307. PMID:17875665 doi:http://dx.doi.org/10.1101/gad.1564307
  7. ↑ Yin H, Lin H. An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster. Nature. 2007 Nov 8;450(7167):304-8. doi: 10.1038/nature06263. Epub 2007 Oct 21. PMID:17952056 doi:http://dx.doi.org/10.1038/nature06263
  8. ↑ 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
  9. ↑ Gangaraju VK, Yin H, Weiner MM, Wang J, Huang XA, Lin H. Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation. Nat Genet. 2011 Feb;43(2):153-8. doi: 10.1038/ng.743. Epub 2010 Dec 26. PMID:21186352 doi:http://dx.doi.org/10.1038/ng.743
  10. ↑ Klenov MS, Sokolova OA, Yakushev EY, Stolyarenko AD, Mikhaleva EA, Lavrov SA, Gvozdev VA. Separation of stem cell maintenance and transposon silencing functions of Piwi protein. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18760-5. doi:, 10.1073/pnas.1106676108. Epub 2011 Nov 7. PMID:22065765 doi:http://dx.doi.org/10.1073/pnas.1106676108
  11. ↑ Sienski G, Donertas D, Brennecke J. Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell. 2012 Nov 21;151(5):964-80. doi: 10.1016/j.cell.2012.10.040. Epub 2012 Nov, 15. PMID:23159368 doi:http://dx.doi.org/10.1016/j.cell.2012.10.040
  12. ↑ Darricarrere N, Liu N, Watanabe T, Lin H. Function of Piwi, a nuclear Piwi/Argonaute protein, is independent of its slicer activity. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1297-302. doi:, 10.1073/pnas.1213283110. Epub 2013 Jan 7. PMID:23297219 doi:http://dx.doi.org/10.1073/pnas.1213283110
  13. ↑ Rozhkov NV, Hammell M, Hannon GJ. Multiple roles for Piwi in silencing Drosophila transposons. Genes Dev. 2013 Feb 15;27(4):400-12. doi: 10.1101/gad.209767.112. Epub 2013 Feb, 7. PMID:23392609 doi:http://dx.doi.org/10.1101/gad.209767.112
  14. ↑ Le Thomas A, Rogers AK, Webster A, Marinov GK, Liao SE, Perkins EM, Hur JK, Aravin AA, Toth KF. Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state. Genes Dev. 2013 Feb 15;27(4):390-9. doi: 10.1101/gad.209841.112. Epub 2013 Feb 7. PMID:23392610 doi:http://dx.doi.org/10.1101/gad.209841.112
  15. ↑ Huang XA, Yin H, Sweeney S, Raha D, Snyder M, Lin H. A major epigenetic programming mechanism guided by piRNAs. Dev Cell. 2013 Mar 11;24(5):502-16. doi: 10.1016/j.devcel.2013.01.023. Epub 2013 , Feb 21. PMID:23434410 doi:http://dx.doi.org/10.1016/j.devcel.2013.01.023
  16. ↑ Ku HY, Gangaraju VK, Qi H, Liu N, Lin H. Tudor-SN Interacts with Piwi Antagonistically in Regulating Spermatogenesis but Synergistically in Silencing Transposons in Drosophila. PLoS Genet. 2016 Jan 25;12(1):e1005813. doi: 10.1371/journal.pgen.1005813., eCollection 2016 Jan. PMID:26808625 doi:http://dx.doi.org/10.1371/journal.pgen.1005813
  17. ↑ Ilyin AA, Ryazansky SS, Doronin SA, Olenkina OM, Mikhaleva EA, Yakushev EY, Abramov YA, Belyakin SN, Ivankin AV, Pindyurin AV, Gvozdev VA, Klenov MS, Shevelyov YY. Piwi interacts with chromatin at nuclear pores and promiscuously binds nuclear transcripts in Drosophila ovarian somatic cells. Nucleic Acids Res. 2017 Jul 27;45(13):7666-7680. doi: 10.1093/nar/gkx355. PMID:28472469 doi:http://dx.doi.org/10.1093/nar/gkx355
  18. ↑ Lin H, Spradling AC. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development. 1997 Jun;124(12):2463-76. PMID:9199372
  19. ↑ Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev. 1998 Dec 1;12(23):3715-27. PMID:9851978
  20. ↑ Yamaguchi S, Oe A, Nishida KM, Yamashita K, Kajiya A, Hirano S, Matsumoto N, Dohmae N, Ishitani R, Saito K, Siomi H, Nishimasu H, Siomi MC, Nureki O. Crystal structure of Drosophila Piwi. Nat Commun. 2020 Feb 12;11(1):858. doi: 10.1038/s41467-020-14687-1. PMID:32051406 doi:http://dx.doi.org/10.1038/s41467-020-14687-1

6kr6, resolution 2.90Å

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