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Title: A conserved mechanism for binding of p53 DNA-Binding domain and Anti-Apoptotic Bcl-2 family proteins
Authors: Lee, Dong-Hwa
Ha, Ji-Hyang
Kim, Yul
Jang, Mi
Park, Sung Jean
Yoon, Ho Sup
Kim, Eun-Hee
Bae, Kwang-Hee
Park, Byoung Chul
Park, Sung Goo
Yi, Gwan-Su
Chi, Seung-Wook
Keywords: DRNTU::Science::Biological sciences
Bcl-2 Family Proteins
Issue Date: 2014
Source: Lee, D.-H., Ha, J.-H., Kim, Y., Jang, M., Park, S. J., Yoon, H. S., . . . Chi, S.-W. (2014). A Conserved Mechanism for Binding of p53 DNA-Binding Domain and Anti-Apoptotic Bcl-2 Family Proteins. Molecules and Cells, 37(3), 264-269. doi:10.14348/molcells.2014.0001
Series/Report no.: Molecules and Cells
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 DNA-binding 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.
ISSN: 1016-8478
DOI: 10.14348/molcells.2014.0001
Rights: © 2014 The Korean Society for Molecular and Cellular Biology. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (
Fulltext Permission: open
Fulltext Availability: With Fulltext
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