3CO6

Crystal Structure of FoxO1 DBD Bound to DBE1 DNA

Summary for 3CO6

• Entry DOI: 10.2210/pdb3co6/pdb
• Related: 3CO7 3COA
• Descriptor: DNA (5'-D(*DTP*DGP*DGP*DTP*DTP*DTP*DGP*DTP*DTP*DTP*DAP*DCP*DCP*DTP*DTP*DG)-3'), DNA (5'-D(*DCP*DAP*DAP*DGP*DGP*DTP*DAP*DAP*DAP*DCP*DAP*DAP*DAP*DCP*DCP*DA)-3'), Forkhead box protein O1, ... (6 entities in total)
• Functional Keywords: winged helix, forkhead domain, chromosomal rearrangement, cytoplasm, dna-binding, nucleus, phosphoprotein, proto-oncogene, transcription, transcription regulation, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q12778
• Total number of polymer chains: 3
• Total formula weight: 21100.50

Authors

Brent, M.M.,Anand, R.,Marmorstein, R. (deposition date: 2008-03-27, release date: 2008-09-16, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)