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PubMed · 14960327

Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR.

Andrew M Petros·Angelo Gunasekera·Nan Xu·Edward T Olejniczak·Stephen W Fesik
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Abstract

p53 exerts its tumor suppressor activity through both transcription-dependent and transcription-independent processes. Although the transcription-dependent activity of p53 has been extensively studied, the mechanism for transcription-independent p53-mediated tumor suppression is less well known. Recently, it was reported that p53 can directly induce mitochondrial permeabilization and promote apoptosis. This occurs through complexation of the DNA-binding region of p53 with the anti-apoptotic proteins Bcl-x(L) and Bcl-2 (Mihara, M. et al. (2003) Mol. Cell 11, 577-590). Using nuclear magnetic resonance (NMR) spectroscopy we show that the interaction surface on p53 involves the same region that is used by the protein to contact DNA. The p53-binding site on Bcl-x(L) consists of the carboxy-terminus of the first alpha-helix, the loop between alpha3 and alpha4, and the loop between alpha5 and alpha6 of Bcl-x(L). Furthermore, the interaction of p53 with Bcl-x(L) is blocked by the binding of a 25-residue peptide derived from the BH3 region of the pro-apoptotic protein referred to as Bad.

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Binding SitesCarrier ProteinsDNA, ComplementaryGene LibraryHumansModels, MolecularNuclear Magnetic Resonance, BiomolecularPeptide FragmentsTumor Suppressor Protein p53bcl-Associated Death ProteinJournal Article

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Andrew M Petros, Angelo Gunasekera, Nan Xu, Edward T Olejniczak, Stephen W Fesik. 2004-02-13. Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR.. https://doi.org/10.1016/s0014-5793(04)00059-6

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