3G73

Structure of the FOXM1 DNA binding

3G73 の概要

• エントリーDOI: 10.2210/pdb3g73/pdb
• 分子名称: Forkhead box protein M1, DNA (5'-D(P*AP*AP*AP*TP*TP*GP*TP*TP*TP*AP*TP*AP*AP*AP*CP*AP*GP*CP*CP*CP*G)-3'), DNA (5'-D(P*TP*TP*CP*GP*GP*GP*CP*TP*GP*TP*TP*TP*AP*TP*AP*AP*AP*CP*AP*AP*T)-3'), ... (5 entities in total)
• 機能のキーワード: dna-binding domain, forkhead transcription factors, foxm1, winged helix, forkhead, transcription regulation, transcription-dna complex, activator, dna-binding, nucleus, phosphoprotein, transcription, transcription/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q08050
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 46132.72

構造登録者

Littler, D.R.,Perrakis, A.,Hibbert, R.G.,Medema, R.H. (登録日: 2009-02-09, 公開日: 2009-03-03, 最終更新日: 2023-11-01)

主引用文献

Littler, D.R.,Alvarez-Fernandez, M.,Stein, A.,Hibbert, R.G.,Heidebrecht, T.,Aloy, P.,Medema, R.H.,Perrakis, A.
Structure of the FoxM1 DNA-recognition domain bound to a promoter sequence
Nucleic Acids Res., 2010

PubMed Abstract: FoxM1 is a member of the Forkhead family of transcription factors and is implicated in inducing cell proliferation and some forms of tumorigenesis. It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence. The affinity of the isolated FoxM1 DNA-binding domain for this site is in the micromolar range, lower than observed for other Forkhead proteins. To explain these FoxM1 features, we determined the crystal structure of its DNA-binding domain in complex with a tandem recognition sequence. FoxM1 adopts the winged-helix fold, typical of the Forkhead family. Neither 'wing' of the fold however, makes significant contacts with the DNA, while the second, C-terminal, wing adopts an unusual ordered conformation across the back of the molecule. The lack of standard DNA-'wing' interactions may be a reason for FoxM1's relatively low affinity. The role of the 'wings' is possibly undertaken by other FoxM1 regions outside the DBD, that could interact with the target DNA directly or mediate interactions with other binding partners. Finally, we were unable to show a clear preference for tandem consensus site recognition in DNA-binding, transcription activation or bioinformatics analysis; FoxM1's moniker, 'Trident', is not supported by our data.

PubMed: 20360045
DOI: 10.1093/nar/gkq194

実験手法

X-RAY DIFFRACTION (2.21 Å)