SNAP output for PDB entry 6ako [SNAP web server]

PDB-id

6ako; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

X-ray (2.396 Å)

Summary

Crystal structure of foxc2 dbd bound to dbe2 DNA

Reference

Chen X, Wei H, Li J, Liang X, Dai S, Jiang L, Guo M, Qu L, Chen Z, Chen L, Chen Y (2019): "Structural basis for DNA recognition by FOXC2." Nucleic Acids Res., 47, 3752-3764. doi: 10.1093/nar/gkz077.

Abstract

The FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. The FOXC2-DBD adopts the winged-helix fold with helix H3 contributing to all the base specific contacts, while the N-terminus, wing 1, and the C-terminus of FOXC2-DBD all make additional contacts with the phosphate groups of DNA. Our structural, biochemical, and bioinformatics analyses allow us to revise the previously proposed DNA recognition mechanism and provide a model of DNA binding for the FOXC proteins. In addition, our structural analysis and accompanying biochemical assays provide a molecular basis for understanding disease-causing mutations in FOXC1 and FOXC2.