9HPJ

Cryo-EM structure of DDB1dB-CRBN-MRT-0031619, conformation 2

これはPDB形式変換不可エントリーです。

9HPJ の概要

• エントリーDOI: 10.2210/pdb9hpj/pdb
• 関連するPDBエントリー: 9HPI
• EMDBエントリー: 52331
• 分子名称: DNA damage-binding protein 1, Protein cereblon, ZINC ION, ... (4 entities in total)
• 機能のキーワード: targeted protein degradation, molecular glue, ubiquitin proteasome system, crbn, ubiquitin ligase, ligase
• 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: 186949.38

構造登録者

Langousis, G.,Hunkeler, M.,Chami, M.,Quan, C.,Townson, S.,Bonenfant, D. (登録日: 2024-12-13, 公開日: 2025-12-03)

主引用文献

Langousis, G.,Gainza, P.,Hunkeler, M.,Kapsitidou, D.,Donckele, E.J.,Annunziato, S.,Wiedmer, L.,Jones, K.F.M.,DeMarco, B.,Quan, C.,Bunker, R.D.,Lumb, K.J.,Fasching, B.,Castle, J.C.,Townson, S.A.,Bonenfant, D.
A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation.
Nat Commun, 16:10157-10157, 2025

PubMed Abstract: Cereblon (CRBN) is an E3 ubiquitin ligase widely harnessed for targeted protein degradation (TPD). We report the discovery of a molecular glue degrader (MGD), MRT-31619, that drives homo-dimerization of CRBN and promotes its fast, potent, and selective degradation by the ubiquitin proteasome system. Interestingly, the cryo-electron microscopy (cryo-EM) structure of the CRBN homodimer reveals a unique mechanism whereby two molecular glues assemble into a helix-like structure and drive ternary complex formation by mimicking a neosubstrate G-loop degron. This CRBN chemical knockout offers a valuable tool to elucidate the molecular mechanism of MGDs, to investigate its endogenous substrates and understand their physiological roles.

PubMed: 41258141
DOI: 10.1038/s41467-025-65094-3

実験手法

ELECTRON MICROSCOPY (3.1 Å)