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Title: Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8

Abstract

The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces 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 vitroandin vivoand 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.

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1354269
Report Number(s):
BNL-112785-2016-JA
Journal ID: ISSN 0270-7306
DOE Contract Number:  
SC00112704
Resource Type:
Journal Article
Journal Name:
Molecular and Cellular Biology
Additional Journal Information:
Journal Volume: 36; Journal Issue: 6; Journal ID: ISSN 0270-7306
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Kumar, Nallani Vijay, Yang, Jianbo, Pillai, Jitesh K., Rawat, Swati, Solano, Carlos, Kumar, Abhay, Grøtli, Morten, Stemmler, Timothy L., Rosen, Barry P., and Tamás, Markus J. Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8. United States: N. p., 2015. Web. doi:10.1128/MCB.00842-15.
Kumar, Nallani Vijay, Yang, Jianbo, Pillai, Jitesh K., Rawat, Swati, Solano, Carlos, Kumar, Abhay, Grøtli, Morten, Stemmler, Timothy L., Rosen, Barry P., & Tamás, Markus J. Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8. United States. https://doi.org/10.1128/MCB.00842-15
Kumar, Nallani Vijay, Yang, Jianbo, Pillai, Jitesh K., Rawat, Swati, Solano, Carlos, Kumar, Abhay, Grøtli, Morten, Stemmler, Timothy L., Rosen, Barry P., and Tamás, Markus J. 2015. "Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8". United States. https://doi.org/10.1128/MCB.00842-15.
@article{osti_1354269,
title = {Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8},
author = {Kumar, Nallani Vijay and Yang, Jianbo and Pillai, Jitesh K. and Rawat, Swati and Solano, Carlos and Kumar, Abhay and Grøtli, Morten and Stemmler, Timothy L. and Rosen, Barry P. and Tamás, Markus J.},
abstractNote = {The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeastSaccharomyces 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 vitroandin vivoand 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.},
doi = {10.1128/MCB.00842-15},
url = {https://www.osti.gov/biblio/1354269}, journal = {Molecular and Cellular Biology},
issn = {0270-7306},
number = 6,
volume = 36,
place = {United States},
year = {Mon Dec 28 00:00:00 EST 2015},
month = {Mon Dec 28 00:00:00 EST 2015}
}