6FJ5

New Insights into the Role of DNA Shape on Its Recognition by p53 Proteins (complex p53DBD-AGG-HG)

6FJ5 の概要

• エントリーDOI: 10.2210/pdb6fj5/pdb
• 関連するPDBエントリー: 5MCT 5MCU 5MCV 5MCW 5MF7 5MG7
• 分子名称: Cellular tumor antigen p53, DNA, ZINC ION, ... (5 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 104031.23

構造登録者

Golovenko, D.,Rozenberg, H.,Shakked, Z. (登録日: 2018-01-20, 公開日: 2018-06-27, 最終更新日: 2024-01-17)

主引用文献

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

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: 30057026
DOI: 10.1016/j.str.2018.06.006

実験手法

X-RAY DIFFRACTION (2.051 Å)