9B9V

Cryo-EM structure of the ZBTB9 BTB domain filament

9B9V の概要

• エントリーDOI: 10.2210/pdb9b9v/pdb
• EMDBエントリー: 44391
• 分子名称: Zinc finger and BTB domain-containing protein 9 (1 entity in total)
• 機能のキーワード: btb domain, transcription factor, zbtb protein, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 271431.45

構造登録者

Park, J.,Hunkeler, M.,Fischer, E.S. (登録日: 2024-04-03, 公開日: 2024-07-24)

主引用文献

Park, P.M.C.,Park, J.,Brown, J.,Hunkeler, M.,Roy Burman, S.S.,Donovan, K.A.,Yoon, H.,Nowak, R.P.,Slabicki, M.,Ebert, B.L.,Fischer, E.S.
Polymerization of ZBTB transcription factors regulates chromatin occupancy.
Mol.Cell, 84:2511-2524.e8, 2024

PubMed Abstract: BCL6, an oncogenic transcription factor (TF), forms polymers in the presence of a small-molecule molecular glue that stabilizes a complementary interface between homodimers of BCL6's broad-complex, tramtrack, and bric-à-brac (BTB) domain. The BTB domains of other proteins, including a large class of TFs, have similar architectures and symmetries, raising the possibility that additional BTB proteins self-assemble into higher-order structures. Here, we surveyed 189 human BTB proteins with a cellular fluorescent reporter assay and identified 18 ZBTB TFs that show evidence of polymerization. Through biochemical and cryoelectron microscopy (cryo-EM) studies, we demonstrate that these ZBTB TFs polymerize into filaments. We found that BTB-domain-mediated polymerization of ZBTB TFs enhances chromatin occupancy within regions containing homotypic clusters of TF binding sites, leading to repression of target genes. Our results reveal a role of higher-order structures in regulating ZBTB TFs and suggest an underappreciated role for TF polymerization in modulating gene expression.

PubMed: 38996460
DOI: 10.1016/j.molcel.2024.06.010

実験手法

ELECTRON MICROSCOPY (8.1 Å)