7DVD

The crystal structure of p53 DNA binding domain and PUMA complex

Summary for 7DVD

• Entry DOI: 10.2210/pdb7dvd/pdb
• Descriptor: Cellular tumor antigen p53, Bcl-2-binding component 3, isoforms 1/2, ZINC ION, ... (4 entities in total)
• Functional Keywords: p53 puma bh3 peptide complex, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 94853.81

Authors

Han, C.W.,Lee, H.N.,Jeong, M.S.,Jang, S.B. (deposition date: 2021-01-13, release date: 2021-08-04, Last modification date: 2024-10-23)

Primary citation

Han, C.W.,Lee, H.N.,Jeong, M.S.,Park, S.Y.,Jang, S.B.
Structural basis of the p53 DNA binding domain and PUMA complex.
Biochem.Biophys.Res.Commun., 548:39-46, 2021

PubMed Abstract: PUMA (p53-upregulated modulator of apoptosis) is localized in mitochondria and a direct target in p53-mediated apoptosis. p53 elicits mitochondrial apoptosis via transcription-dependent and independent mechanisms. p53 is known to induce apoptosis via the transcriptional induction of PUMA, which encodes proapoptotic BH3-only members of the Bcl-2 protein family. However, the transcription-independent mechanisms of human PUMA remain poorly defined. For example, it is not known whether PUMA interacts directly with the DNA binding domain (DBD: residues 92-293) of p53 in vitro. Here, the structure of the complex between the DBD of p53 and PUMA peptide was elucidated by X-ray crystallography. Isothermal titration calorimetry showed that PUMA peptide binds strongly with p53 DBD, and the crystal structure of p53-PUMA peptide complex revealed it contains four molecules of p53 DBD and one PUMA peptide per asymmetric unit in space group P. PUMA peptide bound to the N-terminal residues of p53 DBD. A cell proliferation assay demonstrated PUMA peptide inhibited the growth of a lung cancer cell line. These results contribute to understanding of the mechanism responsible for p53-mediated apoptosis.

PubMed: 33631672
DOI: 10.1016/j.bbrc.2021.02.049

Experimental method

X-RAY DIFFRACTION (2.59 Å)