Title |
Metallochaperones Regulate Intracellular Copper Levels
|
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Published in |
PLoS Computational Biology, January 2013
|
DOI | 10.1371/journal.pcbi.1002880 |
Pubmed ID | |
Authors |
W. Lee Pang, Amardeep Kaur, Alexander V. Ratushny, Aleksandar Cvetkovic, Sunil Kumar, Min Pan, Adam P. Arkin, John D. Aitchison, Michael W. W. Adams, Nitin S. Baliga |
Abstract |
Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
Russia | 1 | 2% |
Brazil | 1 | 2% |
Unknown | 46 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 13 | 27% |
Researcher | 11 | 22% |
Student > Bachelor | 4 | 8% |
Professor > Associate Professor | 4 | 8% |
Student > Master | 4 | 8% |
Other | 8 | 16% |
Unknown | 5 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 15 | 31% |
Biochemistry, Genetics and Molecular Biology | 14 | 29% |
Computer Science | 3 | 6% |
Chemistry | 3 | 6% |
Environmental Science | 2 | 4% |
Other | 6 | 12% |
Unknown | 6 | 12% |