期刊
ANALYTICAL CHEMISTRY
卷 93, 期 50, 页码 16940-16946出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c04230
关键词
-
资金
- NIH [S10 OD010669]
- University of California, Riverside
- Society of Analytical Chemists of Pittsburgh Starter Grant
This study developed a quantitative proteomics methodology to identify destabilized proteins based on their binding to the human Hsp40 chaperone DNAJB8. Exposure of HEK293T cells to meta-arsenite increased the affinity of certain proteins to DNAJB8, including the pyruvate dehydrogenase complex E1 subunit and several RNA-binding proteins. The platform can be used to investigate the impact of environmental toxins on cellular proteostasis and identify susceptible proteins.
Environmental toxins and toxicants can damage proteins and threaten cellular proteostasis. Most current methodologies to identify misfolded proteins in cells survey the entire proteome for sites of changed reactivity. We describe and apply a quantitative proteomics methodology to identify destabilized proteins based on their binding to the human Hsp40 chaperone DNAJB8. These protein targets are validated by an orthogonal limited proteolysis assay using parallel reaction monitoring. We find that a brief exposure of HEK293T cells to meta-arsenite increases the af inity of two dozen proteins to DNAJB8, including known arsenite-sensitive proteins. In particular, arsenite treatment destabilizes both the pyruvate dehydrogenase complex E1 subunit and several RNA-binding proteins. This platform can be used to explore how environmental toxins impact cellular proteostasis and to identify the susceptible proteome.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据