FOXO4 is a member of the FOXO subgroup of forkhead transcription factors that constitute key components of a conserved signalling pathway that connects growth and stress signals to transcriptional control. Here, the 1.9 Å resolution crystal structure of the DNA-binding domain of human FOXO4 (FOXO4-DBD) bound to a 13 bp DNA duplex containing a FOXO consensus binding sequence is reported. The structure shows a similar recognition of the core sequence as has been shown for two other FOXO proteins. Helix H3 is docked into the major groove and provides all of the base-specific contacts, while the N-terminus and wing W1 make additional contacts with the phosphate groups of DNA. In contrast to other FOXO-DBD-DNA structures, the loop between helices H2 and H3 has a different conformation and participates in DNA binding. In addition, the structure of the FOXO4-DBD-DNA complex suggests that both direct water-DNA base contacts and the unique water-network interactions contribute to FOXO-DBD binding to the DNA in a sequence-specific manner.

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University 12843 Prague Czech Republic

References provided by Crossref.org

Isotopic Depletion Increases the Spatial Resolution of FPOP Top-Down Mass Spectrometry Analysis

FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA

MS-Based Approaches Enable the Structural Characterization of Transcription Factor/DNA Response Element Complex

No magnesium is needed for binding of the stimulator of interferon genes to cyclic dinucleotides

Forkhead Domains of FOXO Transcription Factors Differ in both Overall Conformation and Dynamics

Phosphatidylinositol 4-kinase IIIβ (PI4KB) forms highly flexible heterocomplexes that include ACBD3, 14-3-3, and Rab11 proteins

Structural basis for recognition and repair of the 3'-phosphate by NExo, a base excision DNA repair nuclease from Neisseria meningitidis

Crystal structures of a yeast 14-3-3 protein from Lachancea thermotolerans in the unliganded form and bound to a human lipid kinase PI4KB-derived peptide reveal high evolutionary conservation

Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein

The crystal structure of the phosphatidylinositol 4-kinase IIα

See more in PubMed

PDB
3L2C