6G0R

Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated POLR2A peptide (K775ac/K778ac)

6G0R の概要

• エントリーDOI: 10.2210/pdb6g0r/pdb
• 分子名称: Bromodomain-containing protein 4, DNA-directed RNA polymerase II subunit RPB1, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: bromodomain, transcription, complex
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16382.81

構造登録者

Filippakopoulos, P.,Picaud, S.,Pike, A.C.W.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C. (登録日: 2018-03-19, 公開日: 2018-11-28, 最終更新日: 2024-11-20)

主引用文献

Lambert, J.P.,Picaud, S.,Fujisawa, T.,Hou, H.,Savitsky, P.,Uuskula-Reimand, L.,Gupta, G.D.,Abdouni, H.,Lin, Z.Y.,Tucholska, M.,Knight, J.D.R.,Gonzalez-Badillo, B.,St-Denis, N.,Newman, J.A.,Stucki, M.,Pelletier, L.,Bandeira, N.,Wilson, M.D.,Filippakopoulos, P.,Gingras, A.C.
Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.
Mol. Cell, 73:621-638.e17, 2019

PubMed Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1.

PubMed: 30554943
DOI: 10.1016/j.molcel.2018.11.006

実験手法

X-RAY DIFFRACTION (1.25 Å)