2UZK

Crystal structure of the human FOXO3a-DBD bound to DNA

Summary for 2UZK

• Entry DOI: 10.2210/pdb2uzk/pdb
• Descriptor: FORKHEAD BOX PROTEIN O3A, 5'-D(*CP*TP*AP*TP*GP*TP*AP*AP*AP*CP*AP*AP*C)-3', 5'-D(*GP*TP*TP*GP*TP*TP*TP*AP*CP*AP*TP*AP*G)-3', ... (4 entities in total)
• Functional Keywords: transcription, transcription regulation, chromosomal rearrangement, activator, apoptosis, dna-binding, winged helix, proto-oncogene, forkhead transcription factors, nuclear protein, phosphorylation, dna-binding domain
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm, cytosol: O43524
• Total number of polymer chains: 6
• Total formula weight: 37919.43

Authors

Tsai, K.-L.,Sun, Y.-J.,Huang, C.-Y.,Yang, J.-Y.,Hung, M.-C.,Hsiao, C.-D. (deposition date: 2007-04-30, release date: 2008-05-13, Last modification date: 2023-12-13)

Primary citation

Tsai, K.-L.,Sun, Y.-J.,Huang, C.-Y.,Yang, J.-Y.,Hung, M.-C.,Hsiao, C.-D.
Crystal Structure of the Human Foxo3A-Dbd/DNA Complex Suggests the Effects of Post-Translational Modification.
Nucleic Acids Res., 35:6984-, 2007

PubMed 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.

PubMed: 17940099
DOI: 10.1093/NAR/GKM703

Experimental method

X-RAY DIFFRACTION (2.7 Å)