7BUL

Solution structure of the tandem PH and BSD1 domains of TFIIH p62

7BUL の概要

• エントリーDOI: 10.2210/pdb7bul/pdb
• NMR情報: BMRB: 36340
• 分子名称: General transcription factor IIH subunit 1 (1 entity in total)
• 機能のキーワード: dna repair factor, general transcription factor, nucleotide excision repair, nuclear protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18348.99

構造登録者

Okuda, M.,Nishimura, Y. (登録日: 2020-04-07, 公開日: 2020-12-30, 最終更新日: 2024-05-15)

主引用文献

Okuda, M.,Ekimoto, T.,Kurita, J.I.,Ikeguchi, M.,Nishimura, Y.
Structural and dynamical insights into the PH domain of p62 in human TFIIH.
Nucleic Acids Res., 49:2916-2930, 2021

PubMed Abstract: TFIIH is a crucial transcription and DNA repair factor consisting of the seven-subunit core. The core subunit p62 contains a pleckstrin homology domain (PH-D), which is essential for locating TFIIH at transcription initiation and DNA damage sites, and two BSD (BTF2-like transcription factors, synapse-associated proteins and DOS2-like proteins) domains. A recent cryo-electron microscopy (cryo-EM) structure of human TFIIH visualized most parts of core, except for the PH-D. Here, by nuclear magnetic resonance spectroscopy we have established the solution structure of human p62 PH-D connected to the BSD1 domain by a highly flexible linker, suggesting the flexibility of PH-D in TFIIH. Based on this dynamic character, the PH-D was modeled in the cryo-EM structure to obtain the whole human TFIIH core structure, which indicates that the PH-D moves around the surface of core with a specific but limited spatial distribution; these dynamic structures were refined by molecular dynamics (MD) simulations. Furthermore, we built models, also refined by MD simulations, of TFIIH in complex with five p62-binding partners, including transcription factors TFIIEα, p53 and DP1, and nucleotide excision repair factors XPC and UVSSA. The models explain why the PH-D is crucially targeted by these factors, which use their intrinsically disordered acidic regions for TFIIH recruitment.

PubMed: 33211877
DOI: 10.1093/nar/gkaa1045

実験手法

SOLUTION NMR