3FSH

Crystal structure of the ubiquitin conjugating enzyme Ube2g2 bound to the G2BR domain of ubiquitin ligase gp78

3FSH の概要

• エントリーDOI: 10.2210/pdb3fsh/pdb
• 分子名称: Ubiquitin-conjugating enzyme E2 G2, Autocrine motility factor receptor, isoform 2 (3 entities in total)
• 機能のキーワード: protein-peptide complex, ligase, ubl conjugation pathway, alternative splicing, endoplasmic reticulum, membrane, metal-binding, phosphoprotein, polymorphism, receptor, transmembrane, zinc, zinc-finger
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Endoplasmic reticulum membrane; Multi-pass membrane protein: Q9UKV5
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 41182.06

構造登録者

Tu, D.,Brunger, A.T. (登録日: 2009-01-09, 公開日: 2009-02-10, 最終更新日: 2023-09-06)

主引用文献

Li, W.,Tu, D.,Li, L.,Wollert, T.,Ghirlando, R.,Brunger, A.T.,Ye, Y.
Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2.
Proc.Natl.Acad.Sci.USA, 106:3722-3727, 2009

PubMed Abstract: Lys-48-linked polyubiquitination regulates a variety of cellular processes by targeting ubiquitinated proteins to the proteasome for degradation. Although polyubiquitination had been presumed to occur by transferring ubiquitin molecules, one at a time, from an E2 active site to a substrate, we recently showed that the endoplasmic reticulum-associated RING finger ubiquitin ligase gp78 can mediate the preassembly of Lys-48-linked polyubiquitin chains on the catalytic cysteine of its cognate E2 Ube2g2 and subsequent transfer to a substrate. Active site-linked polyubiquitin chains are detected in cells on Ube2g2 and its yeast homolog Ubc7p, but how these chains are assembled is unclear. Here, we show that gp78 forms an oligomer via 2 oligomerization sites, one of which is a hydrophobic segment located in the gp78 cytosolic domain. We further demonstrate that a gp78 oligomer can simultaneously associate with multiple Ube2g2 molecules. This interaction is mediated by a novel Ube2g2 surface distinct from the predicted RING binding site. Our data suggest that a large gp78-Ube2g2 heterooligomer brings multiple Ube2g2 molecules into close proximity, allowing ubiquitin moieties to be transferred between neighboring Ube2g2s to form active site-linked polyubiquitin chains.

PubMed: 19223579
DOI: 10.1073/pnas.0808564106

実験手法

X-RAY DIFFRACTION (2.76 Å)