8E2A

Human Dis3L2 in complex with hairpin D-U7

8E2A の概要

• エントリーDOI: 10.2210/pdb8e2a/pdb
• 関連するPDBエントリー: 4PMW
• EMDBエントリー: 27830
• 分子名称: DIS3-like exonuclease 2, RNA hairpin D-U7 (2 entities in total)
• 機能のキーワード: 3'-5' exonuclease, ds-rna bound exonuclease, human exonuclease, rna binding protein-rna complex, rna binding protein/rna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 106662.43

構造登録者

Meze, K.,Thomas, D.R.,Joshua-Tor, L. (登録日: 2022-08-14, 公開日: 2023-03-01, 最終更新日: 2024-06-12)

主引用文献

Meze, K.,Axhemi, A.,Thomas, D.R.,Doymaz, A.,Joshua-Tor, L.
A shape-shifting nuclease unravels structured RNA.
Nat.Struct.Mol.Biol., 30:339-347, 2023

PubMed Abstract: RNA turnover pathways ensure appropriate gene expression levels by eliminating unwanted transcripts. Dis3-like 2 (Dis3L2) is a 3'-5' exoribonuclease that plays a critical role in human development. Dis3L2 independently degrades structured substrates, including coding and noncoding 3' uridylated RNAs. While the basis for Dis3L2's substrate recognition has been well characterized, the mechanism of structured RNA degradation by this family of enzymes is unknown. We characterized the discrete steps of the degradation cycle by determining cryogenic electron microscopy structures representing snapshots along the RNA turnover pathway and measuring kinetic parameters for RNA processing. We discovered a dramatic conformational change that is triggered by double-stranded RNA (dsRNA), repositioning two cold shock domains by 70 Å. This movement exposes a trihelix linker region, which acts as a wedge to separate the two RNA strands. Furthermore, we show that the trihelix linker is critical for dsRNA, but not single-stranded RNA, degradation. These findings reveal the conformational plasticity of Dis3L2 and detail a mechanism of structured RNA degradation.

PubMed: 36823385
DOI: 10.1038/s41594-023-00923-x

実験手法

ELECTRON MICROSCOPY (2.8 Å)