9OMF

Cryo-EM structure of neddylated PCMTD1-ELOBC-CUL5-RBX2 (N8-CRL5-PCMTD1)

9OMF の概要

• エントリーDOI: 10.2210/pdb9omf/pdb
• 関連するPDBエントリー: 9OMA
• EMDBエントリー: 70612
• 分子名称: Protein-L-isoaspartate O-methyltransferase domain-containing protein 1, Cullin-5, RING-box protein 2, ... (5 entities in total)
• 機能のキーワード: cul5-ring ubiquitin ligase complex, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 168963.73

構造登録者

Pang, E.Z.,Zhao, B.,Flowers, C.,Oroudjeva, E.,Winters, J.B.,Pandey, V.,Sawaya, M.R.,Wohlschlegel, W.,Loo, J.A.,Rodriguez, J.A.,Clarke, S.G. (登録日: 2025-05-13, 公開日: 2025-06-04, 最終更新日: 2025-12-03)

主引用文献

Pang, E.Z.,Zhao, B.,Flowers, C.,Oroudjeva, E.,Winter, J.B.,Pandey, V.,Sawaya, M.R.,Wohlschlegel, J.,Loo, J.A.,Rodriguez, J.A.,Clarke, S.G.
Structural basis for L-isoaspartyl-containing protein recognition by the human PCMTD1 cullin-RING E3 ubiquitin ligase.
J.Biol.Chem., 301:110735-110735, 2025

PubMed Abstract: A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organismal survival. Although repair through methylation by PCMT1 has been previously shown to suppress L-isoaspartyl accumulation, we provide an additional mechanism for L-isoaspartyl maintenance through PCMTD1, a cullin-RING ligase (CRL). We combined cryo-EM, native mass spectrometry, and biochemical assays to provide insight on how the assembly and architecture of human PCMTD1 in the context of a CRL complex fulfills this alternative mechanism. We show that the PCMTD1 CRL complex specifically binds L-isoaspartyl residues when bound to AdoMet. This work provides evidence for a growing class of E3 ubiquitin ligases that recognizes spontaneous covalent modifications as potential substrates for ubiquitylation and subsequent proteasomal degradation.

PubMed: 40975169
DOI: 10.1016/j.jbc.2025.110735

実験手法

ELECTRON MICROSCOPY (9.72 Å)