9ZED

Cryo-EM structure of the endogenous U2/branchpoint spliceosomal complex (SF3A state 2)

これはPDB形式変換不可エントリーです。

9ZED の概要

• エントリーDOI: 10.2210/pdb9zed/pdb
• 関連するPDBエントリー: 9ZE0 9ZE2 9ZE3 9ZEC
• EMDBエントリー: 74100
• 分子名称: U2 snRNA, Splicing factor 3B subunit 5, Splicing factor 3B subunit 6, ... (14 entities in total)
• 機能のキーワード: spliceosome, tumor suppressor, helicase, dhx15, rbm5, sr140, prespliceosomal a complex, splicing
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 779221.66

構造登録者

Liu, S.,Su, T.,Zhou, Z.H. (登録日: 2025-11-29, 公開日: 2026-04-15)

主引用文献

Liu, S.,Su, T.,Huang, J.,Lin, C.H.,Black, D.L.,Damianov, A.,Zhou, Z.H.
The tumour suppressor RBM5 activates the helicase DHX15 to regulate splicing.
Biorxiv, 2026

PubMed Abstract: Pre-mRNA splicing determines the expressed proteome and is frequently dysregulated in cancer. The tumour-suppressor RBM5 controls an exon network regulating apoptosis, yet its molecular mechanism is elusive. Using in vivo spliceosome capture and cryogenic electron microscopy, we determined structures of precatalytic spliceosomes arrested by RBM5 immediately after U2 snRNP branchpoint recognition. Despite intron diversity, the U2-pre-mRNA duplex, branchpoint adenine, and downstream polypyrimidine tract are well-resolved. RBM5 binds the outer SF3B1 HEAT surface and performs dual functions: First, its helix-loop-helix motif and upstream zinc-finger domain sterically block tri-snRNP and Prp8 docking and prevent progression to pre-B and B complexes; Second, its G-patch activates DHX15 and places this DExH-box helicase on the pre-mRNA as it exits SF3B1, poised for branch helix unwinding. DHX15 binding to SF3B1 is facilitated by U2SURP/SR140, which engages SF3B1 near RBM5's helix-loop-helix. Functional assays confirm that disruption of the RBM5 interfaces with either DHX15 or SF3B1 inhibit exon repression. Mutations at these regulatory interfaces are common in cancer genomes and predicted to disrupt its regulation of apoptotic isoforms. Thus, RBM5 acts as a dual-action spliceosome gatekeeper that couples helicase activation with physical stalling to enforce tumour-suppressive alternative splicing programmes.

PubMed: 41929118
DOI: 10.64898/2026.03.26.714623

実験手法

ELECTRON MICROSCOPY (3.94 Å)