6LBI

Crystal Structure of FOXO1-DBD homodimer bound to a palindromic DNA sequence

Summary for 6LBI

• Entry DOI: 10.2210/pdb6lbi/pdb
• Descriptor: IRE0, Forkhead box protein O1 (2 entities in total)
• Functional Keywords: transcription factor, foxo1, protein-dna complex, dna binding, dna binding protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 116122.95

Authors

Li, J.,Dai, S.Y.,Chen, Y.H. (deposition date: 2019-11-14, release date: 2021-02-10, Last modification date: 2023-11-22)

Primary citation

Li, J.,Dai, S.,Chen, X.,Liang, X.,Qu, L.,Jiang, L.,Guo, M.,Zhou, Z.,Wei, H.,Zhang, H.,Chen, Z.,Chen, L.,Chen, Y.
Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.
Nucleic Acids Res., 49:3573-3583, 2021

PubMed Abstract: Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors.

PubMed: 33577686
DOI: 10.1093/nar/gkab086

Experimental method

X-RAY DIFFRACTION (3.067 Å)