6FJ5
New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins (complex p53DBD-AGG-HG)
Summary for 6FJ5
Entry DOI | 10.2210/pdb6fj5/pdb |
Related | 5MCT 5MCU 5MCV 5MCW 5MF7 5MG7 |
Descriptor | Cellular tumor antigen p53, DNA, ZINC ION, ... (5 entities in total) |
Functional Keywords | transcription, p53, transcription factor, dna binding, dna recognition, hoogsteen base-pairing, transcription regulation, apoptosis, biological rhythms, cell cycle, nucleus, tumor suppressor, antigen ny-co-13, phosphoprotein |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 6 |
Total formula weight | 104031.23 |
Authors | Golovenko, D.,Rozenberg, H.,Shakked, Z. (deposition date: 2018-01-20, release date: 2018-06-27, Last modification date: 2024-01-17) |
Primary citation | Golovenko, D.,Brauning, B.,Vyas, P.,Haran, T.E.,Rozenberg, H.,Shakked, Z. New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins. Structure, 26:1237-1250.e6, 2018 Cited by PubMed Abstract: 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. PubMed: 30057026DOI: 10.1016/j.str.2018.06.006 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.051 Å) |
Structure validation
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