New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins
| Autor: | Dmitrij Golovenko, Haim Rozenberg, Zippora Shakked, Tali E. Haran, Bastian Bräuning, Pratik Vyas |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular DNA repair Base pair Protein Conformation Cell Cycle Proteins Response Elements law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Structural Biology law Transcription (biology) Ribonucleotide Reductases Humans Molecular Biology Transcription factor Binding Sites Gadd45 Chemistry Protein Stability Nuclear Proteins Hydrogen Bonding DNA Kinetics 030104 developmental biology P53 protein Biophysics Suppressor Nucleic Acid Conformation Tumor Suppressor Protein p53 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Structure (London, England : 1993). 26(9) |
| ISSN: | 1878-4186 |
| Popis: | The tumor suppressor p53 acts as a transcription factor recognizing diverse DNA response elements (REs). Previous structural studies of p53-DNA complexes revealed non-canonical Hoogsteen geometry of A/T base pairs at conserved CATG motifs leading to changes in DNA shape and its interface with p53. To study the effects of DNA shape on binding characteristics, we designed REs with modified base pairs "locked" into either Hoogsteen or Watson-Crick form. Here we present crystal structures of these complexes and their thermodynamic and kinetic parameters, demonstrating that complexes with Hoogsteen base pairs are stabilized relative to those with all-Watson-Crick base pairs. CATG motifs are abundant in p53REs such as GADD45 and p53R2 related to cell-cycle arrest and DNA repair. The high-resolution structures of these complexes validate their propensity to adopt the unique Hoogsteen-induced structure, thus providing insights into the functional role of DNA shape and broadening the mechanisms that contribute to DNA recognition by proteins. |
| Databáze: | OpenAIRE |
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