8UAH

Structure of BACH1 BTB domain-bound FBXL17 ubiquitin ligase

8UAH の概要

• エントリーDOI: 10.2210/pdb8uah/pdb
• EMDBエントリー: 42064
• 分子名称: F-box/LRR-repeat protein 17, Transcription regulator protein BACH1 (2 entities in total)
• 機能のキーワード: f-box protein, fbxo22, bach1, ligase
• 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: 58849.87

構造登録者

Shi, H.,Cao, S.,Zheng, N. (登録日: 2023-09-21, 公開日: 2024-11-06, 最終更新日: 2025-05-14)

主引用文献

Cao, S.,Garcia, S.F.,Shi, H.,James, E.I.,Kito, Y.,Shi, H.,Mao, H.,Kaisari, S.,Rona, G.,Deng, S.,Goldberg, H.V.,Ponce, J.,Ueberheide, B.,Lignitto, L.,Guttman, M.,Pagano, M.,Zheng, N.
Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress.
Cell, 187:7568-7584.e22, 2024

PubMed Abstract: Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i.e., degrons. Here, we show that BACH1, a transcription repressor of antioxidant response genes, features two distinct unconventional degrons encrypted in the quaternary structure of its homodimeric BTB domain. These two degrons are both functionalized by oxidative stress and are deciphered by two complementary E3s. FBXO22 recognizes a degron constructed by the BACH1 BTB domain dimer interface, which is unmasked from transcriptional co-repressors after oxidative stress releases BACH1 from chromatin. When this degron is impaired by oxidation, a second BACH1 degron manifested by its destabilized BTB dimer is probed by a pair of FBXL17 proteins that remodels the substrate into E3-bound monomers for ubiquitination. Our findings highlight the multidimensionality of protein degradation signals and the functional complementarity of different ubiquitin ligases targeting the same substrate.

PubMed: 39504958
DOI: 10.1016/j.cell.2024.10.012

実験手法

ELECTRON MICROSCOPY (3.3 Å)