4KIT

Crystal structure of human Brr2 in complex with the Prp8 Jab1/MPN domain

4KIT の概要

• エントリーDOI: 10.2210/pdb4kit/pdb
• 分子名称: U5 small nuclear ribonucleoprotein 200 kDa helicase, Pre-mRNA-processing-splicing factor 8, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: reca domain, winged helix domain, sec63 unit, jab1/mpn domain, pre-mrna splicing, atp binding, rna binding, ubiquitin binding, rna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus: O75643; Nucleus speckle (By similarity): Q6P2Q9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 231525.49

構造登録者

Wahl, M.C.,Wandersleben, T.,Santos, K.F. (登録日: 2013-05-02, 公開日: 2013-06-05, 最終更新日: 2023-09-20)

主引用文献

Mozaffari-Jovin, S.,Wandersleben, T.,Santos, K.F.,Will, C.L.,Luhrmann, R.,Wahl, M.C.
Inhibition of RNA helicase Brr2 by the C-terminal tail of the spliceosomal protein Prp8.
Science, 341:80-84, 2013

PubMed Abstract: The Ski2-like RNA helicase Brr2 is a core component of the spliceosome that must be tightly regulated to ensure correct timing of spliceosome activation. Little is known about mechanisms of regulation of Ski2-like helicases by protein cofactors. Here we show by crystal structure and biochemical analyses that the Prp8 protein, a major regulator of the spliceosome, can insert its C-terminal tail into Brr2's RNA-binding tunnel, thereby intermittently blocking Brr2's RNA-binding, adenosine triphosphatase, and U4/U6 unwinding activities. Inefficient Brr2 repression is the only recognizable phenotype associated with certain retinitis pigmentosa-linked Prp8 mutations that map to its C-terminal tail. Our data show how a Ski2-like RNA helicase can be reversibly inhibited by a protein cofactor that directly competes with RNA substrate binding.

PubMed: 23704370
DOI: 10.1126/science.1237515

実験手法

X-RAY DIFFRACTION (3.598 Å)