Crystal Structure of FOXC2 in Complex with DNA Target
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. Her...
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Veröffentlicht in: | ACS omega 2019-06, Vol.4 (6), p.10906-10914 |
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Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | 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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ISSN: | 2470-1343 2470-1343 |
DOI: | 10.1021/acsomega.9b00756 |