Motif orientation matters: Structural characterization of TEAD1 recognition of genomic DNA
| Autor: | Karel Valis, Daniel Kavan, Michal Rosůlek, Jan Fiala, Daniele Fabris, Petr Novák, Jiří Černý, Růžena Filandrová, Josef Chmelík, Lukáš Slavata, Petr Man, Tomáš Chum, Marek Cebecauer |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Jurkat cells
03 medical and health sciences chemistry.chemical_compound Jurkat Cells Structural Biology Humans Binding site Nucleotide Motifs Molecular Biology Transcription factor Gene TEAD1 030304 developmental biology 0303 health sciences Chemistry 030302 biochemistry & molecular biology Nuclear Proteins TEA Domain Transcription Factors DNA Cell biology DNA-Binding Proteins Molecular Docking Simulation genomic DNA Human genome Protein Binding Transcription Factors |
| Zdroj: | Structure |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/j.str.2020.11.018 |
| Popis: | TEAD transcription factors regulate gene expression through interactions with DNA and other proteins. They are crucial for the development of eukaryotic organisms and to control the expression of genes involved mostly in cell proliferation and differentiation; however, their deregulation can lead to tumorigenesis. To study the interactions of TEAD1 with M-CAT motifs and their inverted versions, the KD of each complex was determined, and H/D exchange, quantitative chemical cross-linking, molecular docking, and smFRET were utilized for structural characterization. ChIP-qPCR was employed to correlate the results with a cell line model. The results obtained showed that although the inverted motif has 10× higher KD, the same residues were affected by the presence of M-CAT in both orientations. Molecular docking and smFRET revealed that TEAD1 binds the inverted motif rotated 180°. In addition, the inverted motif was proven to be occupied by TEAD1 in Jurkat cells, suggesting that the low-affinity binding sites present in the human genome may possess biological relevance. |
| Databáze: | OpenAIRE |
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