8CH6

Structure of a late-stage activated spliceosome (BAqr) arrested with a dominant-negative Aquarius mutant (state B complex).

これはPDB形式変換不可エントリーです。

8CH6 の概要

• エントリーDOI: 10.2210/pdb8ch6/pdb
• EMDBエントリー: 16658
• 分子名称: Small nuclear ribonucleoprotein E, Splicing factor 3B subunit 1, PHD finger-like domain-containing protein 5A, ... (53 entities in total)
• 機能のキーワード: activated spliceosome, aquarius, prp2, splicing
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 59
• 化学式量合計: 3668283.05

構造登録者

Cretu, C.,Schmitzova, J.,Pena, V. (登録日: 2023-02-07, 公開日: 2023-05-10, 最終更新日: 2024-07-24)

主引用文献

Schmitzova, J.,Cretu, C.,Dienemann, C.,Urlaub, H.,Pena, V.
Structural basis of catalytic activation in human splicing.
Nature, 617:842-850, 2023

PubMed Abstract: Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated B and the branching-competent B spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16). However, because PRP2 is observed only at the periphery of spliceosomes, its function has remained elusive. Here we show that catalytic activation occurs in two ATP-dependent stages driven by two helicases: PRP2 and Aquarius. The role of Aquarius in splicing has been enigmatic. Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate-the B complex-found halfway through the catalytic activation process. The cryogenic electron microscopy structure of B reveals how PRP2 and Aquarius remodel B and B, respectively. Notably, PRP2 translocates along the intron while it strips away the RES complex, opens the SF3B1 clamp and unfastens the branch helix. Translocation terminates six nucleotides downstream of the branch site through an assembly of PPIL4, SKIP and the amino-terminal domain of PRP2. Finally, Aquarius enables the dissociation of PRP2, plus the SF3A and SF3B complexes, which promotes the relocation of the branch duplex for catalysis. This work elucidates catalytic activation in human splicing, reveals how a DEAH helicase operates and provides a paradigm for how helicases can coordinate their activities.

PubMed: 37165190
DOI: 10.1038/s41586-023-06049-w

実験手法

ELECTRON MICROSCOPY (5.9 Å)