5H7S

Structural basis of the flanking zinc-finger motifs crucial for the E3 ligase activity of the LNX1 RING domain

5H7S の概要

• エントリーDOI: 10.2210/pdb5h7s/pdb
• 関連するPDBエントリー: 5H7R
• 分子名称: Ubiquitin-like 1, E3 ubiquitin-protein ligase LNX, Ubiquitin-conjugating enzyme E2 N, ... (4 entities in total)
• 機能のキーワード: ring, ubiquitin, e3 ligase, zinc finger motif, protein binding-ligase-transferase complex, protein binding/ligase/transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Ubiquitin: Cytoplasm : P0CG47; Cytoplasm : Q8TBB1; Nucleus : P61088
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 81180.22

構造登録者

Nayak, D.,Sivaraman, J. (登録日: 2016-11-21, 公開日: 2017-11-29, 最終更新日: 2023-11-08)

主引用文献

Nayak, D.,Sivaraman, J.
Structure of LNX1:Ubc13~Ubiquitin Complex Reveals the Role of Additional Motifs for the E3 Ligase Activity of LNX1.
J. Mol. Biol., 430:1173-1188, 2018

PubMed Abstract: LNX1 (ligand of numb protein-X1) is a RING and PDZ domain-containing E3 ubiquitin ligase that ubiquitinates human c-Src kinase. Here, we report the identification and structure of the ubiquitination domain of LNX1, the identification of Ubc13/Ube2V2 as a functional E2 in vitro, and the structural and functional studies of the Ubc13~Ub intermediate in complex with the ubiquitination domain of LNX1. The RING domain of LNX1 is embedded between two zinc-finger motifs (Zn-RING-Zn), both of which are crucial for its ubiquitination activity. In the heterodimeric complex, the ubiquitin of one monomer shares more buried surface area with LNX1 of the other monomer and these interactions are unique and essential for catalysis. This study reveals how the LNX1 RING domain is structurally and mechanistically dependent on other motifs for its E3 ligase activity, and describes how dimeric LNX1 recruits ubiquitin-loaded Ubc13 for Ub transfer via E3 ligase-mediated catalysis.

PubMed: 29496391
DOI: 10.1016/j.jmb.2018.02.016

実験手法

X-RAY DIFFRACTION (3.49 Å)