5guh

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Crystal structure of silkworm PIWI-clade Argonaute Siwi bound to piRNA

Structural highlights

5guh is a 2 chain structure with sequence from Bombyx mori. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:MG, OMU
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SIWI_BOMMO Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity (PubMed:19460866, PubMed:27693359). Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells (PubMed:19460866, PubMed:25558067, PubMed:27693359). Its presence in oocytes suggests that it may participate in similar functions during oogenesis in females (PubMed:18191035). Acts via the piRNA metabolic process, which mediates 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 (PubMed:19460866, PubMed:25558067, PubMed:27693359). 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:19460866, PubMed:25558067, PubMed:27693359). Recognizes piRNAs containing a phosphate at the 5'-end and a 2'-O-methylation modification at the 3'-end (PubMed:27693359). Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias) and a complementary adenosine in the target (t1A bias) (PubMed:24757166, PubMed:27693359). Plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle: antisense piRNA-bound Siwi and sense piRNA-bound Ago3 reciprocally cleave complementary transcripts, to couple the amplification of piRNAs with the repression of transposable elements. In this process Siwi acts as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto Ago3 (PubMed:27693359). In this process, Siwi requires the RNA unwinding activity of the RNA helicase Vasa for the release of the cleavage products (PubMed:25558067).[1] [2] [3] [4] [5]

Publication Abstract from PubMed

PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 A resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5' and 3' ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5'-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing.

Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA.,Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O Cell. 2016 Oct 6;167(2):484-497.e9. doi: 10.1016/j.cell.2016.09.002. Epub 2016, Sep 29. PMID:27693359[6]

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

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References

  1. Kawaoka S, Minami K, Katsuma S, Mita K, Shimada T. Developmentally synchronized expression of two Bombyx mori Piwi subfamily genes, SIWI and BmAGO3 in germ-line cells. Biochem Biophys Res Commun. 2008 Mar 21;367(4):755-60. PMID:18191035 doi:10.1016/j.bbrc.2008.01.013
  2. Kawaoka S, Hayashi N, Suzuki Y, Abe H, Sugano S, Tomari Y, Shimada T, Katsuma S. The Bombyx ovary-derived cell line endogenously expresses PIWI/PIWI-interacting RNA complexes. RNA. 2009 Jul;15(7):1258-64. PMID:19460866 doi:10.1261/rna.1452209
  3. Cora E, Pandey RR, Xiol J, Taylor J, Sachidanandam R, McCarthy AA, Pillai RS. The MID-PIWI module of Piwi proteins specifies nucleotide- and strand-biases of piRNAs. RNA. 2014 Apr 22. PMID:24757166 doi:http://dx.doi.org/10.1261/rna.044701.114
  4. Nishida KM, Iwasaki YW, Murota Y, Nagao A, Mannen T, Kato Y, Siomi H, Siomi MC. Respective functions of two distinct Siwi complexes assembled during PIWI-interacting RNA biogenesis in Bombyx germ cells. Cell Rep. 2015 Jan 13;10(2):193-203. PMID:25558067 doi:10.1016/j.celrep.2014.12.013
  5. Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O. Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA. Cell. 2016 Oct 6;167(2):484-497.e9. doi: 10.1016/j.cell.2016.09.002. Epub 2016, Sep 29. PMID:27693359 doi:http://dx.doi.org/10.1016/j.cell.2016.09.002
  6. Matsumoto N, Nishimasu H, Sakakibara K, Nishida KM, Hirano T, Ishitani R, Siomi H, Siomi MC, Nureki O. Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA. Cell. 2016 Oct 6;167(2):484-497.e9. doi: 10.1016/j.cell.2016.09.002. Epub 2016, Sep 29. PMID:27693359 doi:http://dx.doi.org/10.1016/j.cell.2016.09.002

Contents


PDB ID 5guh

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