期刊
PLOS BIOLOGY
卷 19, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pbio.3001208
关键词
-
资金
- Army Research Office [W911NF-12-1-0390]
- Center for Modeling Complex Interactions - National Institute of General Medical Sciences [P20 GM104420]
- National Science Foundation EPSCoR TrackII [OIA1736253]
- BEACON Center for the Study of Evolution in Action (parent NSF) [DBI0939454]
- Department of Organismic and Evolutionary Biology at Harvard University
- INBRE Undergraduate Research Fellowship (parent NIH) [P20GM103408]
- National Institutes of Health [NIH P30 GM103324]
- Office of Nuclear Energy of the U.S. DOE [DE-AC07-05ID14517]
- Nuclear Science User Facilities [DE-AC07-05ID14517]
EfgA is a protein that serves as a formaldehyde sensor in methylotrophic bacteria, quickly halting cell growth in response to elevated formaldehyde levels. Its heterologous expression in Escherichia coli enhances formaldehyde resistance, suggesting potential widespread and conserved interaction partners. EfgA represents a unique stress response mechanism in bacteria by directly sensing toxic intracellular metabolites without enzymatic detoxification.
Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage.
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