Summary information and primary citation

PDB-id
6o3t; SNAP-derived features in text and JSON formats; DNAproDB
Class
gene regulation-DNA
Method
X-ray (3.06 Å)
Summary
Structural basis of foxc2 and DNA interactions
Reference
Li S, Pradhan L, Ashur S, Joshi A, Nam HJ (2019): "Crystal Structure of FOXC2 in Complex with DNA Target." Acs Omega, 4, 10906-10914. doi: 10.1021/acsomega.9b00756.
Abstract
Forkhead transcription factor C2 (FOXC2) is a transcription factor regulating vascular and lymphatic development, and its mutations are linked to lymphedema-distichiasis syndrome. FOXC2 is also a crucial regulator of the epithelial-mesenchymal transition processes essential for tumor metastasis. Here, we report the crystal structure of the FOXC2-DNA-binding domain in complex with its cognate DNA. The crystal structure provides the basis of DNA sequence recognition by FOXC2 for the T/CAAAC motif. Helix 3 makes the majority of the DNA-protein interactions and confers the DNA sequence specificity. The computational energy calculation results also validate the structural observations. The FOXC2 and DNA complex structure provides a detailed picture of protein and DNA interactions, which allows us to predict its DNA recognition specificity and impaired functions in mutants identified in human patients.

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