A conserved mechanism for binding of p53 DNA-binding domain and anti-apoptotic Bcl-2 family proteins

Cited 19 time in scopus
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Title
A conserved mechanism for binding of p53 DNA-binding domain and anti-apoptotic Bcl-2 family proteins
Author(s)
Dong Hwa Lee; Ji Hyang Ha; Y Kim; Mi Jang; S J Park; H S Yoon; E H Kim; Kwang-Hee BaeByoung Chul ParkSung Goo Park; G S Yi; Seung-Wook Chi
Bibliographic Citation
Molecules and Cells, vol. 37, no. 3, pp. 264-269
Publication Year
2014
Abstract
The molecular interaction between tumor suppressor p53 and the anti-apoptotic Bcl-2 family proteins plays an essential role in the transcription-independent apoptotic pathway of p53. In this study, we investigated the binding of p53 DNA-binding domain (p53DBD) with the anti-apoptotic Bcl-2 family proteins, Bcl-w, Mcl-1, and Bcl-2, using GST pull-down assay and NMR spectroscopy. The GST pull-down assays and NMR experiments demonstrated the direct binding of the p53DBD with Bcl-w, Mcl-1, and Bcl-2. Further, NMR chemical shift perturbation data showed that Bcl-w and Mcl-1 bind to the positively charged DNAbinding surface of p53DBD. Noticeably, the refined structural models of the complexes between p53DBD and Bcl-w, Mcl-1, and Bcl-2 showed that the binding mode of p53DBD is highly conserved among the anti-apoptotic Bcl-2 family proteins. Furthermore, the chemical shift perturbations on Bcl-w, Mcl-1, and Bcl-2 induced by p53DBD binding occurred not only at the p53DBD-binding acidic region but also at the BH3 peptide-binding pocket, which suggests an allosteric conformational change similar to that observed in Bcl-XL. Taken altogether, our results revealed a structural basis for a conserved binding mechanism between p53DBD and the anti-apoptotic Bcl-2 family proteins, which shed light on to the molecular understanding of the transcription-independent apoptosis pathway of p53.
Keyword
ApoptosisBcl-2 family proteinsBinding mechanismDNA-binding domainp53
ISSN
1016-8478
Publisher
South Korea
DOI
http://dx.doi.org/10.14348/molcells.2014.0001
Type
Article
Appears in Collections:
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Division of Biomedical Research > 1. Journal Articles
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