7CBY

Structure of FOXG1 DNA binding domain bound to DBE2 DNA site

Summary for 7CBY

• Entry DOI: 10.2210/pdb7cby/pdb
• Descriptor: DNA (5'-D(*TP*CP*TP*TP*GP*TP*TP*TP*AP*CP*AP*TP*TP*TP*TP*G)-3'), DNA (5'-D(*CP*AP*AP*AP*AP*TP*GP*TP*AP*AP*AP*CP*AP*AP*GP*A)-3'), Forkhead box protein G1, ... (5 entities in total)
• Functional Keywords: foxg1, forkhead box, transcription factors, foxg1 syndrome, dbe2, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 22383.83

Authors

Dai, S.Y.,Li, J.,Chen, Y.H. (deposition date: 2020-06-15, release date: 2020-10-28, Last modification date: 2023-11-29)

Primary citation

Dai, S.,Li, J.,Zhang, H.,Chen, X.,Guo, M.,Chen, Z.,Chen, Y.
Structural Basis for DNA Recognition by FOXG1 and the Characterization of Disease-causing FOXG1 Mutations.
J.Mol.Biol., 432:6146-6156, 2020

PubMed Abstract: 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 Å. FOXG1-DBD adopts a typical winged helix fold. Compared to those of other FOX-DBD/DBE2 structures, the N terminus, H3 helix and wing2 region of FOXG1-DBD exhibit differences in DNA recognition. The FOXG1-DBD wing2 region adopts a unique architecture composed of two β-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.

PubMed: 33058871
DOI: 10.1016/j.jmb.2020.10.007

Experimental method

X-RAY DIFFRACTION (1.646 Å)