3CO7

Crystal Structure of FoxO1 DBD Bound to DBE2 DNA

3CO7 の概要

• エントリーDOI: 10.2210/pdb3co7/pdb
• 関連するPDBエントリー: 3CO6 3COA
• 分子名称: DNA (5'-D(*DTP*DCP*DTP*DTP*DGP*DTP*DTP*DTP*DAP*DCP*DAP*DTP*DTP*DTP*DTP*DG)-3'), DNA (5'-D(*DCP*DAP*DAP*DAP*DAP*DTP*DGP*DTP*DAP*DAP*DAP*DCP*DAP*DAP*DGP*DA)-3'), Forkhead box protein O1, ... (4 entities in total)
• 機能のキーワード: winged helix, forkhead domain, chromosomal rearrangement, cytoplasm, dna-binding, nucleus, phosphoprotein, proto-oncogene, transcription, transcription regulation, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q12778
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 45892.35

構造登録者

Brent, M.M.,Anand, R.,Marmorstein, R. (登録日: 2008-03-27, 公開日: 2008-09-16, 最終更新日: 2024-02-21)

主引用文献

Brent, M.M.,Anand, R.,Marmorstein, R.
Structural Basis for DNA Recognition by FoxO1 and Its Regulation by Posttranslational Modification.
Structure, 16:1407-1416, 2008

PubMed Abstract: FoxO transcription factors regulate the transcription of genes that control metabolism, cellular proliferation, stress tolerance, and possibly life span. A number of posttranslational modifications within the forkhead DNA-binding domain regulate FoxO-mediated transcription. We describe the crystal structures of FoxO1 bound to three different DNA elements and measure the change in FoxO1-DNA affinity with acetylation and phosphorylation. The structures reveal additional contacts and increased DNA distortion for the highest affinity DNA site. The flexible wing 2 region of the forkhead domain was not observed in the structures but is necessary for DNA binding, and we show that p300 acetylation in wing 2 reduces DNA affinity. We also show that MST1 phosphorylation of FoxO1 prevents high-affinity DNA binding. The observation that FoxO-DNA affinity varies between response elements and with posttranslational modifications suggests that modulation of FoxO-DNA affinity is an important component of FoxO regulation in health and misregulation in disease.

PubMed: 18786403
DOI: 10.1016/j.str.2008.06.013

実験手法

X-RAY DIFFRACTION (2.91 Å)