4HJE

Crystal structure of p53 core domain in complex with DNA

4HJE の概要

• エントリーDOI: 10.2210/pdb4hje/pdb
• 分子名称: Cellular tumor antigen p53, DNA (5'-D(*TP*CP*AP*CP*AP*AP*GP*TP*TP*AP*GP*AP*GP*AP*CP*AP*AP*GP*CP*CP*T)-3'), DNA (5'-D(*AP*GP*GP*CP*TP*TP*GP*TP*CP*TP*CP*TP*AP*AP*CP*TP*TP*GP*TP*GP*A)-3'), ... (5 entities in total)
• 機能のキーワード: tumor suppressor, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 103264.50

構造登録者

Chen, Y.,Chen, L. (登録日: 2012-10-12, 公開日: 2013-07-17, 最終更新日: 2024-02-28)

主引用文献

Chen, Y.,Zhang, X.,Dantas Machado, A.C.,Ding, Y.,Chen, Z.,Qin, P.Z.,Rohs, R.,Chen, L.
Structure of p53 binding to the BAX response element reveals DNA unwinding and compression to accommodate base-pair insertion.
Nucleic Acids Res., 41:8368-8376, 2013

PubMed Abstract: The p53 core domain binds to response elements (REs) that contain two continuous half-sites as a cooperative tetramer, but how p53 recognizes discontinuous REs is not well understood. Here we describe the crystal structure of the p53 core domain bound to a naturally occurring RE located at the promoter of the Bcl-2-associated X protein (BAX) gene, which contains a one base-pair insertion between the two half-sites. Surprisingly, p53 forms a tetramer on the BAX-RE that is nearly identical to what has been reported on other REs with a 0-bp spacer. Each p53 dimer of the tetramer binds in register to a half-site and maintains the same protein-DNA interactions as previously observed, and the two dimers retain all the protein-protein contacts without undergoing rotation or translation. To accommodate the additional base pair, the DNA is deformed and partially disordered around the spacer region, resulting in an apparent unwinding and compression, such that the interactions between the dimers are maintained. Furthermore, DNA deformation within the p53-bound BAX-RE is confirmed in solution by site-directed spin labeling measurements. Our results provide a structural insight into the mechanism by which p53 binds to discontinuous sites with one base-pair spacer.

PubMed: 23836939
DOI: 10.1093/nar/gkt584

実験手法

X-RAY DIFFRACTION (1.907 Å)