8R2D

Integrator cleavage module assembly intermediate

8R2D の概要

• エントリーDOI: 10.2210/pdb8r2d/pdb
• EMDBエントリー: 18839
• 分子名称: BRCA1-associated ATM activator 1, Integrator complex subunit 9, Integrator complex subunit 11, ... (5 entities in total)
• 機能のキーワード: chaperone, integrator complex, nuclear import, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 341058.11

構造登録者

Sabath, K.,Qiu, C.,Jonas, S. (登録日: 2023-11-03, 公開日: 2024-07-31, 最終更新日: 2025-07-02)

主引用文献

Sabath, K.,Qiu, C.,Jonas, S.
Assembly mechanism of Integrator's RNA cleavage module.
Mol.Cell, 84:2882-2899.e10, 2024

PubMed Abstract: The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'-processing of non-coding RNAs. For both activities, Integrator requires endonuclease activity that is harbored by an RNA cleavage module consisting of INTS4-9-11. How correct assembly of Integrator modules is achieved remains unknown. Here, we show that BRAT1 and WDR73 are critical biogenesis factors for the human cleavage module. They maintain INTS9-11 inactive during maturation by physically blocking the endonuclease active site and prevent premature INTS4 association. Furthermore, BRAT1 facilitates import of INTS9-11 into the nucleus, where it is joined by INTS4. Final BRAT1 release requires locking of the mature cleavage module conformation by inositol hexaphosphate (IP). Our data explain several neurodevelopmental disorders caused by BRAT1, WDR73, and INTS11 mutations as Integrator assembly defects and reveal that IP is an essential co-factor for cleavage module maturation.

PubMed: 39032489
DOI: 10.1016/j.molcel.2024.06.032

実験手法

ELECTRON MICROSCOPY (3.9 Å)