6O3T

Structural basis of FOXC2 and DNA interactions

Summary for 6O3T

• Entry DOI: 10.2210/pdb6o3t/pdb
• Descriptor: Forkhead box protein C2, DNA (5'-D(*AP*AP*AP*TP*TP*GP*TP*TP*TP*AP*TP*AP*AP*AP*CP*AP*GP*CP*CP*CP*G)-3'), DNA (5'-D(*TP*TP*CP*GP*GP*GP*CP*TP*GP*TP*TP*TP*AP*TP*AP*AP*AP*CP*AP*AP*T)-3') (3 entities in total)
• Functional Keywords: forkhead transcription factor dna binding, gene regulation, gene regulation-dna complex, gene regulation/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 35416.21

Authors

Nam, H.-J.,Li, S. (deposition date: 2019-02-27, release date: 2020-01-15, Last modification date: 2023-10-11)

Primary citation

Li, S.,Pradhan, L.,Ashur, S.,Joshi, A.,Nam, H.J.
Crystal Structure of FOXC2 in Complex with DNA Target.
Acs Omega, 4:10906-10914, 2019

PubMed 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.

PubMed: 31460188
DOI: 10.1021/acsomega.9b00756

Experimental method

X-RAY DIFFRACTION (3.06 Å)