9L5T

Cryo-EM structure of the thermophile spliceosome (state B*Q2)

これはPDB形式変換不可エントリーです。

9L5T の概要

• エントリーDOI: 10.2210/pdb9l5t/pdb
• EMDBエントリー: 62843
• 分子名称: U2 snRNA, Putative pre-mRNA splicing protein, Suppressor of forked domain-containing protein, ... (42 entities in total)
• 機能のキーワード: spilceosome, dhx15, dhx35, gpatch1, splicing/rna, splicing-rna complex
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719) (Thermochaetoides thermophila); 詳細
• タンパク質・核酸の鎖数: 42
• 化学式量合計: 2246736.16

構造登録者

Li, Y.,Fischer, P.,Wang, M.,Yuan, R.,Meng, W.,Luehrmann, R.,Lau, B.,Hurt, E.,Cheng, J. (登録日: 2024-12-23, 公開日: 2025-03-12, 最終更新日: 2025-04-16)

主引用文献

Li, Y.,Fischer, P.,Wang, M.,Zhou, Q.,Song, A.,Yuan, R.,Meng, W.,Chen, F.X.,Luhrmann, R.,Lau, B.,Hurt, E.,Cheng, J.
Structural insights into spliceosome fidelity: DHX35-GPATCH1- mediated rejection of aberrant splicing substrates.
Cell Res., 35:296-308, 2025

PubMed Abstract: The spliceosome, a highly dynamic macromolecular assembly, catalyzes the precise removal of introns from pre-mRNAs. Recent studies have provided comprehensive structural insights into the step-wise assembly, catalytic splicing and final disassembly of the spliceosome. However, the molecular details of how the spliceosome recognizes and rejects suboptimal splicing substrates remained unclear. Here, we show cryo-electron microscopy structures of spliceosomal quality control complexes from a thermophilic eukaryote, Chaetomium thermophilum. The spliceosomes, henceforth termed B*, are stalled at a catalytically activated state but prior to the first splicing reaction due to an aberrant 5' splice site conformation. This state is recognized by G-patch protein GPATCH1, which is docked onto PRP8-EN and -RH domains and has recruited the cognate DHX35 helicase to its U2 snRNA substrate. In B*, DHX35 has dissociated the U2/branch site helix, while the disassembly helicase DHX15 is docked close to its U6 RNA 3'-end substrate. Our work thus provides mechanistic insights into the concerted action of two spliceosomal helicases in maintaining splicing fidelity by priming spliceosomes that are bound to aberrant splice substrates for disassembly.

PubMed: 40016598
DOI: 10.1038/s41422-025-01084-w

実験手法

ELECTRON MICROSCOPY (3.5 Å)