Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity

Hudie Wei, Haolan Wang, Genxin Wang, Lingzhi Qu, Longying Jiang, Shuyan Dai, Xiaojuan Chen, Ye Zhang, Zhuchu Chen, Youjun Li, Ming Guo () and Yongheng Chen ()
Additional contact information
Hudie Wei: Central South University
Haolan Wang: Central South University
Genxin Wang: Wuhan University
Lingzhi Qu: Central South University
Longying Jiang: Central South University
Shuyan Dai: Central South University
Xiaojuan Chen: Central South University
Ye Zhang: Central South University
Zhuchu Chen: Central South University
Youjun Li: Wuhan University
Ming Guo: Central South University
Yongheng Chen: Central South University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-40087-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40087-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-40087-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().