期刊
STRUCTURE
卷 29, 期 4, 页码 345-+出版社
CELL PRESS
DOI: 10.1016/j.str.2020.11.018
关键词
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资金
- Czech Science Foundation [16-24309S]
- Ministry of Education of the Czech Republic [LH15010, LQ1604, LO1509]
- European Commission H2020 (EPIC-XS) [823839]
- Charles University Grant Agency [1618218]
- Czech Academy of Sciences [RVO61388971]
- European Regional Development Funds [CZ.1.05/1.1.00/02.0109 BIOCEV]
- Czech Infrastructure for Integrative Structural Biology (MEYS CR) [LM2015043]
- FP7 WeNMR European e-Infrastructure project [261572]
- H2020 West-Life European e-Infrastructure project [675858]
- EU (Operational Program Prague-Competitiveness Project) [CZ.2.16/3.1.00/24023]
TEAD transcription factors regulate gene expression through interactions with DNA and other proteins. Research findings suggest that TEAD1 can bind to the inverted version of the M-CAT motif, and that inverted motifs in the human genome may have biological relevance.
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 K-D 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 103higher K-D, 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 degrees. 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.
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