The p53 C Terminus Controls Site-Specific DNA Binding and Promotes Structural Changes within the Central DNA Binding Domain
| Autor: | James J. Manfredi, Ella Freulich, Andrew Zupnick, Tamar Kahan, Inbal Shamir, Itamar Simon, Oleg Laptenko, Melissa Mattia, William A. Freed-Pastor, Idit Shiff, Noam Kadouri, Carol Prives |
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| Rok vydání: | 2015 |
| Předmět: |
HMG-box
Biology Ligands Response Elements Article 03 medical and health sciences 0302 clinical medicine Humans Binding site Molecular Biology Transcription factor Sequence Deletion 030304 developmental biology 0303 health sciences Binding Sites DNA Cell Biology DNA-binding domain Molecular biology Protein Structure Tertiary Cell biology DNA binding site 030220 oncology & carcinogenesis CTD Tumor Suppressor Protein p53 Binding domain P53 binding |
| Zdroj: | Molecular Cell. 57:1034-1046 |
| ISSN: | 1097-2765 |
| Popis: | DNA binding by numerous transcription factors including the p53 tumor suppressor protein constitutes a vital early step in transcriptional activation. While the role of the central core DNA binding domain (DBD) of p53 in site-specific DNA binding has been established, the contribution of the sequence-independent C-terminal domain (CTD) is still not well understood. We investigated the DNA-binding properties of a series of p53 CTD variants using a combination of in vitro biochemical analyses and in vivo binding experiments. Our results provide several unanticipated and interconnected findings. First, the CTD enables DNA binding in a sequence-dependent manner that is drastically altered by either its modification or deletion. Second, dependence on the CTD correlates with the extent to which the p53 binding site deviates from the canonical consensus sequence. Finally, the CTD enables stable formation of p53-DNA complexes to divergent binding sites via DNA-induced conformational changes within the DBD itself. |
| Databáze: | OpenAIRE |
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