Metallochaperones regulate intracellular copper levels.
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC3551603?pdf=render |
| _version_ | 1818505465595691008 |
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| author | 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 |
| author_facet | 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 |
| author_sort | W Lee Pang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T21:51:09Z |
| format | Article |
| id | doaj.art-b27661cffb7b450c92bdf63b96fee4a3 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-10T21:51:09Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-b27661cffb7b450c92bdf63b96fee4a32022-12-22T01:32:11ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582013-01-0191e100288010.1371/journal.pcbi.1002880Metallochaperones regulate intracellular copper levels.W Lee PangAmardeep KaurAlexander V RatushnyAleksandar CvetkovicSunil KumarMin PanAdam P ArkinJohn D AitchisonMichael W W AdamsNitin S BaligaCopper (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.http://europepmc.org/articles/PMC3551603?pdf=render |
| spellingShingle | 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 Metallochaperones regulate intracellular copper levels. PLoS Computational Biology |
| title | Metallochaperones regulate intracellular copper levels. |
| title_full | Metallochaperones regulate intracellular copper levels. |
| title_fullStr | Metallochaperones regulate intracellular copper levels. |
| title_full_unstemmed | Metallochaperones regulate intracellular copper levels. |
| title_short | Metallochaperones regulate intracellular copper levels. |
| title_sort | metallochaperones regulate intracellular copper levels |
| url | http://europepmc.org/articles/PMC3551603?pdf=render |
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