7KX7

Cryo-EM structure of Ephydatia fluviatilis PiwiA-piRNA complex

7KX7 の概要

• エントリーDOI: 10.2210/pdb7kx7/pdb
• EMDBエントリー: 23061
• 分子名称: Piwi-A, RNA (5'-R(P*UP*CP*UP*CP*AP*GP*(OMC))-3'), MAGNESIUM ION (3 entities in total)
• 機能のキーワード: rnaseh, protein-rna complex, rna binding protein, pirna binding, paz piwi domain protein, hydrolase, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Ephydatia fluviatilis; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96311.02

構造登録者

Anzelon, T.A.,Chowdhury, S.,Lander, G.C.,MacRae, I.J. (登録日: 2020-12-03, 公開日: 2021-07-14, 最終更新日: 2024-05-29)

主引用文献

Anzelon, T.A.,Chowdhury, S.,Hughes, S.M.,Xiao, Y.,Lander, G.C.,MacRae, I.J.
Structural basis for piRNA targeting.
Nature, 597:285-289, 2021

PubMed Abstract: PIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations. The targeting of transposable elements by PIWI has been compared to mRNA target recognition by Argonaute proteins, which use microRNA (miRNA) guides, but the extent to which piRNAs resemble miRNAs is not known. Here we present cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs, and a biochemical analysis of target recognition. Mirroring Argonaute, PIWI identifies targets using the piRNA seed region. However, PIWI creates a much weaker seed so that stable target association requires further piRNA-target pairing, making piRNAs less promiscuous than miRNAs. Beyond the seed, the structure of PIWI facilitates piRNA-target pairing in a manner that is tolerant of mismatches, leading to long-lived PIWI-piRNA-target interactions that may accumulate on transposable-element transcripts. PIWI ensures targeting fidelity by physically blocking the propagation of piRNA-target interactions in the absence of faithful seed pairing, and by requiring an extended piRNA-target duplex to reach an endonucleolytically active conformation. PIWI proteins thereby minimize off-targeting cellular mRNAs while defending against evolving genomic threats.

PubMed: 34471284
DOI: 10.1038/s41586-021-03856-x

実験手法

ELECTRON MICROSCOPY (3.8 Å)