9QWZ

Cryo-EM structure of the human UBR4/KCMF1/CALM1 complex (BP focused refinement)

これはPDB形式変換不可エントリーです。

9QWZ の概要

• エントリーDOI: 10.2210/pdb9qwz/pdb
• EMDBエントリー: 53431
• 分子名称: E3 ubiquitin-protein ligase KCMF1, E3 ubiquitin-protein ligase UBR4 (2 entities in total)
• 機能のキーワード: ubiquitin ligase, protein quality control, 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: 619036.65

構造登録者

Grabarczyk, D.B.,Clausen, T. (登録日: 2025-04-15, 公開日: 2025-09-03, 最終更新日: 2025-09-17)

主引用文献

Grabarczyk, D.B.,Ehrmann, J.F.,Murphy, P.,Yang, W.S.,Kurzbauer, R.,Bell, L.E.,Deszcz, L.,Neuhold, J.,Schleiffer, A.,Shulkina, A.,Lee, J.,Shin, J.S.,Meinhart, A.,Versteeg, G.A.,Zavodszky, E.,Song, H.K.,Hegde, R.S.,Clausen, T.
Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.
Science, 389:909-914, 2025

PubMed Abstract: Eukaryotic cells have evolved sophisticated quality control mechanisms to eliminate aggregation-prone proteins that compromise cellular health. Central to this defense is the ubiquitin-proteasome system, where UBR4 acts as an essential E4 ubiquitin ligase, amplifying degradation marks on defective proteins. Cryo-electron microscopy analysis of UBR4 in complex with its cofactors KCMF1 and CALM1 reveals a massive 1.3-megadalton ring structure, featuring a central substrate-binding arena and flexibly attached catalytic units. Our structure shows how UBR4 binds substrate and extends lysine-48-specific ubiquitin chains. Efficient substrate targeting depends on both preubiquitination and specific N-degrons, with KCMF1 acting as a key substrate filter. The architecture of the E4 megacomplex is conserved across eukaryotes, but species-specific adaptations allow UBR4 to perform its precisely tuned quality control function in diverse cellular environments.

PubMed: 40875847
DOI: 10.1126/science.adv9309

実験手法

ELECTRON MICROSCOPY (4.8 Å)