9MLC

Pol II-DSIF-SPT6-PAF1c-TFIIS-IWS1-ELOF1-LEDGF-nucleosome activated elongation complex Composite map T

9MLC の概要

• エントリーDOI: 10.2210/pdb9mlc/pdb
• EMDBエントリー: 48353
• 分子名称: DNA-directed RNA polymerase II subunit RPB1, DNA-directed RNA polymerases I, II, and III subunit RPABC5, RNA polymerase II subunit J, ... (29 entities in total)
• 機能のキーワード: polymerase, elongation factor, nucleosome, transcription
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 27
• 化学式量合計: 1593946.93

構造登録者

Syau, D.,Farnung, L. (登録日: 2024-12-19, 公開日: 2026-01-21, 最終更新日: 2026-05-27)

主引用文献

Syau, D.,Steinruecke, F.,Roth, S.,Schmid, E.,Adelman, K.,Walter, J.C.,Farnung, L.
Structure and function of IWS1 in transcription elongation.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: Transcription elongation by RNA polymerase II is a tightly regulated process that requires coordinated interactions between transcription elongation factors. IWS1 (Interacts with SPT6) has been implicated as a core elongation factor, but its molecular role remains unclear. We show that the intrinsically disordered C-terminal region of IWS1 contains short linear motifs (SLiMs) that multivalently engage the elongation machinery. Using cryo-electron microscopy, we map SLiMs in IWS1 that interact with Pol II subunits RPB1, RPB2, and RPB5, as well as elongation factors DSIF, SPT6, and ELOF1. Functional assays demonstrate that distinct IWS1 SLiMs specify IWS1 recruitment and IWS1-dependent transcription stimulation. IWS1 recruitment to the transcription elongation complex depends on association via the RPB1 jaw and binding of downstream DNA. Transcription elongation stimulation requires interactions with the RPB2 lobe and ELOF1. We identify other transcription elongation factors including ELOA and RECQL5 that bind the RPB1 jaw and demonstrate that IWS1 protects the activated transcription elongation complex from RECQL5 inhibition. We also reveal the binding of the histone reader and IWS1 interactor LEDGF to a transcribed downstream nucleosome. Our findings establish IWS1 as a modular scaffold that helps organize the transcription elongation complex, illustrating how disordered regions regulate transcription elongation.

PubMed: 42134803
DOI: 10.1093/nar/gkag357

実験手法

ELECTRON MICROSCOPY (2.4 Å)