6S53

Crystal structure of TRIM21 RING domain in complex with an isopeptide-linked Ube2N~ubiquitin conjugate

6S53 の概要

• エントリーDOI: 10.2210/pdb6s53/pdb
• 分子名称: Ubiquitin-conjugating enzyme E2 N, Polyubiquitin-C, E3 ubiquitin-protein ligase TRIM21, ... (6 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, e2 conjugating enzyme, intracellular immunity, viral defence, trim21, ube2n, ubiquitin, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 141491.91

構造登録者

Kiss, L.,Boland, A.,Neuhaus, D.,James, L.C. (登録日: 2019-06-30, 公開日: 2019-09-11, 最終更新日: 2024-01-24)

主引用文献

Kiss, L.,Zeng, J.,Dickson, C.F.,Mallery, D.L.,Yang, J.C.,McLaughlin, S.H.,Boland, A.,Neuhaus, D.,James, L.C.
A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases.
Nat Commun, 10:4502-4502, 2019

PubMed Abstract: The cytosolic antibody receptor TRIM21 possesses unique ubiquitination activity that drives broad-spectrum anti-pathogen targeting and underpins the protein depletion technology Trim-Away. This activity is dependent on formation of self-anchored, K63-linked ubiquitin chains by the heterodimeric E2 enzyme Ube2N/Ube2V2. Here we reveal how TRIM21 facilitates ubiquitin transfer and differentiates this E2 from other closely related enzymes. A tri-ionic motif provides optimally distributed anchor points that allow TRIM21 to wrap an Ube2N~Ub complex around its RING domain, locking the closed conformation and promoting ubiquitin discharge. Mutation of these anchor points inhibits ubiquitination with Ube2N/Ube2V2, viral neutralization and immune signalling. We show that the same mechanism is employed by the anti-HIV restriction factor TRIM5 and identify spatially conserved ionic anchor points in other Ube2N-recruiting RING E3s. The tri-ionic motif is exclusively required for Ube2N but not Ube2D1 activity and provides a generic E2-specific catalysis mechanism for RING E3s.

PubMed: 31582740
DOI: 10.1038/s41467-019-12388-y

実験手法

X-RAY DIFFRACTION (2.8 Å)