Summary information and primary citation
- PDB-id
-
2uzk;
DSSR-derived features in text and
JSON formats
- Class
- transcription
- Method
- X-ray (2.7 Å)
- Summary
- Crystal structure of the human foxo3a-dbd bound to
DNA
- Reference
-
Tsai K-L, Sun Y-J, Huang C-Y, Yang J-Y, Hung M-C, Hsiao
C-D (2007): "Crystal
Structure of the Human Foxo3A-Dbd/DNA Complex Suggests
the Effects of Post-Translational Modification."
Nucleic Acids Res., 35, 6984.
doi: 10.1093/NAR/GKM703.
- Abstract
- FOXO3a is a transcription factor of the FOXO family.
The FOXO proteins participate in multiple signaling
pathways, and their transcriptional activity is regulated
by several post-translational mechanisms, including
phosphorylation, acetylation and ubiquitination. Because
these post-translational modification sites are located
within the C-terminal basic region of the FOXO DNA-binding
domain (FOXO-DBD), it is possible that these
post-translational modifications could alter the
DNA-binding characteristics. To understand how FOXO mediate
transcriptional activity, we report here the 2.7 A crystal
structure of the DNA-binding domain of FOXO3a (FOXO3a-DBD)
bound to a 13-bp DNA duplex containing a FOXO consensus
binding sequence (GTAAACA). Based on a unique structural
feature in the C-terminal region and results from
biochemical and mutational studies, our studies may explain
how FOXO-DBD C-terminal phosphorylation by protein kinase B
(PKB) or acetylation by cAMP-response element binding
protein (CBP) can attenuate the DNA-binding activity and
thereby reduce transcriptional activity of FOXO proteins.
In addition, we demonstrate that the methyl groups of
specific thymine bases within the consensus sequence are
important for FOXO3a-DBD recognition of the consensus
binding site.
