8RC4

Structure of Integrator-PP2A complex

8RC4 の概要

• エントリーDOI: 10.2210/pdb8rc4/pdb
• EMDBエントリー: 19047
• 分子名称: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Integrator complex subunit 8, Integrator complex subunit 9, ... (18 entities in total)
• 機能のキーワード: integrator complex, post-termination complex, rna polymerase ii, pol ii, rnapii, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 1435164.97

構造登録者

Fianu, I.,Ochmann, M.,Walshe, J.L.,Cramer, P. (登録日: 2023-12-06, 公開日: 2024-02-07, 最終更新日: 2024-10-16)

主引用文献

Fianu, I.,Ochmann, M.,Walshe, J.L.,Dybkov, O.,Cruz, J.N.,Urlaub, H.,Cramer, P.
Structural basis of Integrator-dependent RNA polymerase II termination.
Nature, 629:219-227, 2024

PubMed Abstract: The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10-INTS13-INTS14-INTS15 module that may use its 'sting' to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator-PP2A complex in an inactive closed conformation reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements.

PubMed: 38570683
DOI: 10.1038/s41586-024-07269-4

実験手法

ELECTRON MICROSCOPY (3.1 Å)