9N1F

Crystal Structure of the Ark2C-Ubc13~Ub-Mms2 complex

9N1F の概要

• エントリーDOI: 10.2210/pdb9n1f/pdb
• 分子名称: E3 ubiquitin-protein ligase ARK2C, Ubiquitin-conjugating enzyme E2 N, Ubiquitin-conjugating enzyme E2 variant 2, ... (6 entities in total)
• 機能のキーワード: ring e3 ligase ubiquitin ptm, ligase, e2~ub conjugate, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 52497.73

構造登録者

Paluda, A.,Middleton, A.J.,Day, C.L. (登録日: 2025-01-26, 公開日: 2025-06-11, 最終更新日: 2025-06-25)

主引用文献

Rossig, C.,Paluda, A.,Chen, R.,Middleton, A.J.,Day, C.L.
Arkadia and Ark2C Promote Substrate Ubiquitylation with Multiple E2 Enzymes.
J.Mol.Biol., 437:169259-169259, 2025

PubMed Abstract: Ubiquitylation is a critical post-translational modification that is required for cell vitality. Attachment of ubiquitin is complex, with the fate of ubiquitylated proteins determined by the length of the attached ubiquitin chains and the nature of the linkage used to build the chains. Many E3 ligases attach ubiquitin chains of different types to substrate proteins in a context specific manner, but the molecular details of how E3 ligases specify chains of different types is poorly understood. Arkadia/RNF111 is a large RING E3 ligase that modifies some substrates with degradative ubiquitin chains, while other substrates are modified with non-degradative ubiquitin chains. Here, using Arkadia and the related E3 ligase, Ark2C, we characterize the RING-E2 complexes that promote assembly of ubiquitin chains of distinct linkages. Our structural studies highlight the conserved nature of the RING-E2 interface, while our binding and activity assays reveal several different E2 enzymes that functionally interact with Ark2C and Arkadia. Using Arkadia, substrate ubiquitylation assays reveal differences in the ability for substrates to be modified, with the E2 enzymes Ubc13 and Ube2K requiring addition of a 'priming' ubiquitin molecule before subsequent modification can occur. We also show that substrates that bind Arkadia tightly are more extensively modified, and that prior substrate ubiquitylation enhances subsequent modification. While further studies will be required to understand how RING-E2 pairing is modulated in cells, this study advances our understanding of E2 recruitment and chain assembly by Arkadia and provides tools that may help dissect cellular function.

PubMed: 40451499
DOI: 10.1016/j.jmb.2025.169259

実験手法

X-RAY DIFFRACTION (2.1 Å)