8HLL

Crystal structure of p53/BCL2 fusion complex (complex 1)

8HLL の概要

• エントリーDOI: 10.2210/pdb8hll/pdb
• 分子名称: Cellular tumor antigen p53, Apoptosis regulator Bcl-2, ZINC ION, ... (4 entities in total)
• 機能のキーワード: apoptosis
• 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: 41382.53

構造登録者

Wei, H.,Guo, M.,Wang, H.,Chen, Y. (登録日: 2022-11-30, 公開日: 2023-07-26, 最終更新日: 2024-05-29)

主引用文献

Wei, H.,Wang, H.,Wang, G.,Qu, L.,Jiang, L.,Dai, S.,Chen, X.,Zhang, Y.,Chen, Z.,Li, Y.,Guo, M.,Chen, Y.
Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity.
Nat Commun, 14:4300-4300, 2023

PubMed Abstract: Mitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor protein p53 triggers transcription-independent apoptosis through direct interactions with BCL-2 family proteins, but the molecular mechanism is not well understood. In this study, we present three crystal structures of p53-DBD in complex with the anti-apoptotic protein BCL-2 at resolutions of 2.3-2.7 Å. The structures show that two loops of p53-DBD penetrate directly into the BH3-binding pocket of BCL-2. Structure-based mutations at the interface impair the p53/BCL-2 interaction. Specifically, the binding sites for p53 and the pro-apoptotic protein Bax in the BCL-2 pocket are mostly identical. In addition, formation of the p53/BCL-2 complex is negatively correlated with the formation of BCL-2 complexes with pro-apoptotic BCL-2 family members. Defects in the p53/BCL-2 interaction attenuate p53-mediated cell apoptosis. Overall, our study provides a structural basis for the interaction between p53 and BCL-2, and suggests a molecular mechanism by which p53 regulates transcription-independent apoptosis by antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family members.

PubMed: 37463921
DOI: 10.1038/s41467-023-40087-2

実験手法

X-RAY DIFFRACTION (2.62 Å)