5ZI6

The RING domain structure of MEX-3C

5ZI6 の概要

• エントリーDOI: 10.2210/pdb5zi6/pdb
• 分子名称: RNA-binding E3 ubiquitin-protein ligase MEX3C, ZINC ION (3 entities in total)
• 機能のキーワード: e3 liagase, ubiquitination, mex-3c, ring domain, ligase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 49487.53

構造登録者

Moududee, S.A.,Tang, Y. (登録日: 2018-03-14, 公開日: 2018-10-24, 最終更新日: 2024-03-27)

主引用文献

Moududee, S.A.,Jiang, Y.,Gilbert, N.,Xie, G.,Xu, Z.,Wu, J.,Gong, Q.,Tang, Y.,Shi, Y.
Structural and functional characterization of hMEX-3C Ring finger domain as an E3 ubiquitin ligase
Protein Sci., 27:1661-1669, 2018

PubMed Abstract: MEX-3C, a novel RNA binding E3 ubiquitin ligases, contains two N-terminal heterogeneous nuclear ribonucleoprotein K homology (KH) domains and C-terminal Ring finger domain. Recent evidence has suggested that human MEX-3C has a strong bondage with carcinogenesis and the MEX-3C-mediated ubiquitination of RIG-I is essential for the antiviral innate immune response. Moreover, the Ring finger domain of MEX-3C could regulate the degradation of HLA-A2 (an MHC-I allotype) mRNA with a novel mechanism. However, the structural basis for the ubiquitination catalyzed by hMEX-3C Ring finger domain remains evasive. In this study, we solved the crystal structure of dimeric Ring finger domain of hMEX-3C and compared it with the complex structure of MDM2/MDMX-UbcH5b-Ub. Our ubiquitination assay demonstrated that the Ring finger domain of hMEX-3C acts as a ubiquitin E3 ligase in vitro, cooperating with specific E2 to mediate ubiquitination. Then, we identified several key residues in Ring finger domain of hMEX-3C possibly involved in the interaction with E2-Ub conjugate and analyzed the E3 ligase activities of wild type and mutants at key sites. Additionally, zinc chelation experiments indicated that the intact structural stability is essential for the self-ubiquitination activity of the Ring finger domain of hMEX-3C. Taken together, our studies provided new insight into the mechanism of the Ring finger domain of hMEX-3C that may play an important role in eliciting antiviral immune responses and therapeutic interventions.

PubMed: 30095198
DOI: 10.1002/pro.3473

実験手法

X-RAY DIFFRACTION (2.2 Å)