7cby

Publication Abstract from PubMed

Forkhead box G1 (FOXG1) is a transcription factor mainly expressed in the brain that plays a critical role in the development and regionalization of the forebrain. Aberrant expression of FOXG1 has implications in FOXG1 syndrome, a serious neurodevelopmental disorder. Here, we report the crystal structure of the FOXG1 DNA-binding domain (DBD) in complex with the forkhead consensus DNA site DBE2 at the resolution of 1.6 A. FOXG1-DBD adopts a typical winged helix fold. Compared to those of other FOX-DBD/DBE2 structures, the N-terminus, H3 helix and wing2region of FOXG1-DBD exhibit differences in DNA recognition. The FOXG1-DBD wing2 region adopts a unique architecture composed of two beta-strands that differs from all other known FOX-DBD wing2 folds. Mutation assays revealed that the disease-causing mutations within the FOXG1-DBD affect DNA binding, protein thermal stability, or both. Our report provides initial insight into how FOXG1 binds DNA and sheds light on how disease-causing mutations in FOXG1-DBD affect its DNA-binding ability.

Structural basis for DNA recognition by FOXG1 and the characterization of disease-causing FOXG1 mutations.,Dai S, Li J, Zhang H, Chen X, Guo M, Chen Z, Chen Y J Mol Biol. 2020 Oct 12. pii: S0022-2836(20)30583-0. doi:, 10.1016/j.jmb.2020.10.007. PMID:33058871^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.