6LBM

Crystal Structure of FOXC2-DBD bound to a palindromic DNA sequence

6LBM の概要

• エントリーDOI: 10.2210/pdb6lbm/pdb
• 分子名称: Forkhead box protein C2, IRE0, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: forkhead transcription, dna binding specificity, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 24620.45

構造登録者

Li, J.,Dai, S.Y. (登録日: 2019-11-14, 公開日: 2021-02-10, 最終更新日: 2023-11-22)

主引用文献

Li, J.,Dai, S.,Chen, X.,Liang, X.,Qu, L.,Jiang, L.,Guo, M.,Zhou, Z.,Wei, H.,Zhang, H.,Chen, Z.,Chen, L.,Chen, Y.
Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.
Nucleic Acids Res., 49:3573-3583, 2021

PubMed Abstract: Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors.

PubMed: 33577686
DOI: 10.1093/nar/gkab086

実験手法

X-RAY DIFFRACTION (2.841 Å)