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
- Issue Date
- 31-Mar-2014
- Publisher
- KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
- Keywords
- apoptosis; Bcl-2 family proteins; binding mechanism; DNA-binding domain; p53
- Citation
- MOLECULES AND CELLS, v.37, no.3, pp.264 - 269
- Journal Title
- MOLECULES AND CELLS
- Volume
- 37
- Number
- 3
- Start Page
- 264
- End Page
- 269
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12770
- DOI
- 10.14348/molcells.2014.0001
- ISSN
- 1016-8478
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 약학대학 > 약학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12770)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.