7V6C

Structure of the Dicer-2-R2D2 heterodimer bound to small RNA duplex

7V6C の概要

• エントリーDOI: 10.2210/pdb7v6c/pdb
• 関連するPDBエントリー: 7V6B
• EMDBエントリー: 31742
• 分子名称: Dicer-2, isoform A, R2D2, RNA (5'-R(P*UP*GP*AP*GP*G)-3'), ... (6 entities in total)
• 機能のキーワード: rna binding protein, ribonuclease, double-stranded rna-binding protein
• 由来する生物種: Drosophila melanogaster (Fruit fly); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 266517.63

構造登録者

Yamaguchi, S.,Nishizawa, T.,Kusakizako, T.,Yamashita, K.,Tomita, A.,Hirano, H.,Nishimasu, H.,Nureki, O. (登録日: 2021-08-20, 公開日: 2022-03-23, 最終更新日: 2024-06-12)

主引用文献

Yamaguchi, S.,Naganuma, M.,Nishizawa, T.,Kusakizako, T.,Tomari, Y.,Nishimasu, H.,Nureki, O.
Structure of the Dicer-2-R2D2 heterodimer bound to a small RNA duplex.
Nature, 607:393-398, 2022

PubMed Abstract: In flies, Argonaute2 (Ago2) and small interfering RNA (siRNA) form an RNA-induced silencing complex to repress viral transcripts. The RNase III enzyme Dicer-2 associates with its partner protein R2D2 and cleaves long double-stranded RNAs to produce 21-nucleotide siRNA duplexes, which are then loaded into Ago2 in a defined orientation. Here we report cryo-electron microscopy structures of the Dicer-2-R2D2 and Dicer-2-R2D2-siRNA complexes. R2D2 interacts with the helicase domain and the central linker of Dicer-2 to inhibit the promiscuous processing of microRNA precursors by Dicer-2. Notably, our structure represents the strand-selection state in the siRNA-loading process, and reveals that R2D2 asymmetrically recognizes the end of the siRNA duplex with the higher base-pairing stability, and the other end is exposed to the solvent and is accessible by Ago2. Our findings explain how R2D2 senses the thermodynamic asymmetry of the siRNA and facilitates the siRNA loading into Ago2 in a defined orientation, thereby determining which strand of the siRNA duplex is used by Ago2 as the guide strand for target silencing.

PubMed: 35768503
DOI: 10.1038/s41586-022-04790-2

実験手法

ELECTRON MICROSCOPY (3.3 Å)