3K9P

The crystal structure of E2-25K and ubiquitin complex

3K9P の概要

• エントリーDOI: 10.2210/pdb3k9p/pdb
• 関連するPDBエントリー: 3K9O
• 分子名称: Ubiquitin-conjugating enzyme E2 K, Ubiquitin (2 entities in total)
• 機能のキーワード: e2-25k, ubiquitin, complex structure, atp-binding, isopeptide bond, ligase, nucleotide-binding, ubl conjugation pathway, nucleus, phosphoprotein, ligase-signaling protein complex, ligase/signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm (By similarity): P61086
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32953.57

構造登録者

Kang, G.B.,Ko, S.,Song, S.M.,Lee, W.,Eom, S.H. (登録日: 2009-10-16, 公開日: 2010-09-08, 最終更新日: 2024-03-20)

主引用文献

Ko, S.,Kang, G.B.,Song, S.M.,Lee, J.-G.,Shin, D.Y.,Yun, J.-H.,Sheng, Y.,Cheong, C.,Jeon, Y.H.,Jung, Y.-K.,Arrowsmith, C.H.,Avvakumov, G.V.,Dhe-Paganon, S.,Yoo, Y.J.,Eom, S.H.,Lee, W.
Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity
J.Biol.Chem., 285:36070-36080, 2010

PubMed Abstract: E2-25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the frameshift mutant of ubiquitin B (UBB(+1)) and has been identified as a crucial factor regulating amyloid-β neurotoxicity. To study the structural basis of the neurotoxicity mediated by the E2-25K-UBB(+1) interaction, we determined the three-dimensional structures of UBB(+1), E2-25K and the E2-25K/ubiquitin, and E2-25K/UBB(+1) complex. The structures revealed that ubiquitin or UBB(+1) is bound to E2-25K via the enzyme MGF motif and residues in α9 of the enzyme. Polyubiquitylation assays together with analyses of various E2-25K mutants showed that disrupting UBB(+1) binding markedly diminishes synthesis of neurotoxic UBB(+1)-anchored polyubiquitin. These results suggest that the interaction between E2-25K and UBB(+1) is critical for the synthesis and accumulation of UBB(+1)-anchored polyubiquitin, which results in proteasomal inhibition and neuronal cell death.

PubMed: 20826778
DOI: 10.1074/jbc.M110.145219

実験手法

X-RAY DIFFRACTION (2.8 Å)