6LHD

Crystal structure of p53/BCL-xL fusion complex

Summary for 6LHD

• Entry DOI: 10.2210/pdb6lhd/pdb
• Descriptor: fusion protein of Bcl-2-like protein 1 and Isoform 6 of Cellular tumor antigen p53, ZINC ION (3 entities in total)
• Functional Keywords: complex, interaction, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 83850.30

Authors

Wei, H.,Chen, Y. (deposition date: 2019-12-07, release date: 2021-03-31, Last modification date: 2023-11-22)

Primary citation

Wei, H.,Qu, L.,Dai, S.,Li, Y.,Wang, H.,Feng, Y.,Chen, X.,Jiang, L.,Guo, M.,Li, J.,Chen, Z.,Chen, L.,Zhang, Y.,Chen, Y.
Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis.
Nat Commun, 12:2280-2280, 2021

PubMed Abstract: The tumor suppressor p53 is mutated in approximately half of all human cancers. p53 can induce apoptosis through mitochondrial membrane permeabilization by interacting with and antagonizing the anti-apoptotic proteins BCL-xL and BCL-2. However, the mechanisms by which p53 induces mitochondrial apoptosis remain elusive. Here, we report a 2.5 Å crystal structure of human p53/BCL-xL complex. In this structure, two p53 molecules interact as a homodimer, and bind one BCL-xL molecule to form a ternary complex with a 2:1 stoichiometry. Mutations at the p53 dimer interface or p53/BCL-xL interface disrupt p53/BCL-xL interaction and p53-mediated apoptosis. Overall, our current findings of the bona fide structure of p53/BCL-xL complex reveal the molecular basis of the interaction between p53 and BCL-xL, and provide insight into p53-mediated mitochondrial apoptosis.

PubMed: 33863900
DOI: 10.1038/s41467-021-22655-6

Experimental method

X-RAY DIFFRACTION (2.499 Å)