Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8
| Autor: | Carlos Solano, Markus J. Tamás, Jianbo Yang, Timothy L. Stemmler, Nallani Vijay Kumar, Jitesh K. Pillai, Abhay Kumar, Barry P. Rosen, Swati Rawat, Morten Grøtli |
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| Rok vydání: | 2016 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Conformational change Saccharomyces cerevisiae Proteins Arsenate Reductases Protein Conformation Saccharomyces cerevisiae Arsenic 03 medical and health sciences chemistry.chemical_compound Transcription (biology) Gene Expression Regulation Fungal Transcriptional regulation Binding site DNA Fungal Molecular Biology Transcription factor 030102 biochemistry & molecular biology biology Membrane Transport Proteins Articles Cell Biology biology.organism_classification Yeast Transcription Factor AP-1 Basic-Leucine Zipper Transcription Factors 030104 developmental biology chemistry Biochemistry DNA Protein Binding |
| Zdroj: | Molecular and Cellular Biology. 36:913-922 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00842-15 |
| Popis: | The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation. |
| Databáze: | OpenAIRE |
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