6GYT

Transcription factor dimerization activates the p300 acetyltransferase

6GYT の概要

• エントリーDOI: 10.2210/pdb6gyt/pdb
• 分子名称: Histone acetyltransferase p300, Histone H4, ZINC ION, ... (5 entities in total)
• 機能のキーワード: p300, cbp, acetyltransferase, chromatin, transcriptional regulation, gene regulation
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 39661.25

構造登録者

Panne, D.,Ortega, E. (登録日: 2018-07-01, 公開日: 2018-10-17, 最終更新日: 2024-11-13)

主引用文献

Ortega, E.,Rengachari, S.,Ibrahim, Z.,Hoghoughi, N.,Gaucher, J.,Holehouse, A.S.,Khochbin, S.,Panne, D.
Transcription factor dimerization activates the p300 acetyltransferase.
Nature, 562:538-544, 2018

PubMed Abstract: The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation.

PubMed: 30323286
DOI: 10.1038/s41586-018-0621-1

実験手法

X-RAY DIFFRACTION (2.5 Å)