4XXB

Crystal structure of human MDM2-RPL11

4XXB の概要

• エントリーDOI: 10.2210/pdb4xxb/pdb
• 分子名称: 60S ribosomal protein L11, E3 ubiquitin-protein ligase Mdm2, IMIDAZOLE, ... (6 entities in total)
• 機能のキーワード: mdm2, rpl11, modpipe model of up, rna binding protein-metal binding protein complex, rna binding protein/metal binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37417.54

構造登録者

Zheng, J.,Chen, Z. (登録日: 2015-01-30, 公開日: 2015-08-12, 最終更新日: 2023-11-08)

主引用文献

Zheng, J.,Lang, Y.,Zhang, Q.,Cui, D.,Sun, H.,Jiang, L.,Chen, Z.,Zhang, R.,Gao, Y.,Tian, W.,Wu, W.,Tang, J.,Chen, Z.
Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation
Genes Dev., 29:1524-1534, 2015

PubMed Abstract: The central region of MDM2 is critical for p53 activation and tumor suppression. Upon ribosomal stress, this region is bound by ribosomal proteins, particularly ribosomal protein L11 (RPL11), leading to MDM2 inactivation and subsequent p53 activation. Here, we solved the complex structure of human MDM2-RPL11 at 2.4 Å. MDM2 extensively interacts with RPL11 through an acidic domain and two zinc fingers. Formation of the MDM2-RPL11 complex induces substantial conformational changes in both proteins. RPL11, unable to bind MDM2 mutants, fails to induce the activation of p53 in cells. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc finger determines RPL11 binding to MDM2 but not its homolog, MDMX. Our results highlight the essential role of the RPL11-MDM2 interaction in p53 activation and tumor suppression and provide a structural basis for potential new anti-tumor drug development.

PubMed: 26220995
DOI: 10.1101/gad.261792.115

実験手法

X-RAY DIFFRACTION (2.4 Å)