SNAP output for PDB entry 3co6 [SNAP web server]

PDB-id

3co6; SNAP-derived features in text and JSON formats; DNAproDB

Class

transcription-DNA

Method

X-ray (2.1 Å)

Summary

Crystal structure of foxo1 dbd bound to dbe1 DNA

Reference

Brent MM, Anand R, Marmorstein R (2008): "Structural Basis for DNA Recognition by FoxO1 and Its Regulation by Posttranslational Modification." Structure, 16, 1407-1416. doi: 10.1016/j.str.2008.06.013.

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.