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7cby

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Structure of FOXG1 DNA binding domain bound to DBE2 DNA site

Structural highlights

7cby is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.646Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FOXG1_HUMAN FOXG1 syndrome due to 14q12 microdeletion;14q11.2 microduplication syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

FOXG1_HUMAN Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.^[1]

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.

References

↑ Tan K, Shaw AL, Madsen B, Jensen K, Taylor-Papadimitriou J, Freemont PS. Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. J Biol Chem. 2003 Jun 6;278(23):20507-13. Epub 2003 Mar 25. PMID:12657635 doi:http://dx.doi.org/10.1074/jbc.M301994200
↑ 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. 2020 Nov 20;432(23):6146-6156. PMID:33058871 doi:10.1016/j.jmb.2020.10.007