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Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force

LmrA is a bacterial ATP-binding cassette (ABC) multidrug exporter that uses metabolic energy to transport ions, cytotoxic drugs, and lipids. Voltage clamping in a Port-a-Patch was used to monitor electrical currents associated with the transport of monovalent cationic HEPES(+) by single-LmrA transpo...

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Detalles Bibliográficos
Autores principales: Agboh, Kelvin, Lau, Calvin H. F., Khoo, Yvonne S. K., Singh, Himansha, Raturi, Sagar, Nair, Asha V., Howard, Julie, Chiapello, Marco, Feret, Renata, Deery, Michael J., Murakami, Satoshi, van Veen, Hendrik W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155054/
https://www.ncbi.nlm.nih.gov/pubmed/30255140
http://dx.doi.org/10.1126/sciadv.aas9365
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author Agboh, Kelvin
Lau, Calvin H. F.
Khoo, Yvonne S. K.
Singh, Himansha
Raturi, Sagar
Nair, Asha V.
Howard, Julie
Chiapello, Marco
Feret, Renata
Deery, Michael J.
Murakami, Satoshi
van Veen, Hendrik W.
author_facet Agboh, Kelvin
Lau, Calvin H. F.
Khoo, Yvonne S. K.
Singh, Himansha
Raturi, Sagar
Nair, Asha V.
Howard, Julie
Chiapello, Marco
Feret, Renata
Deery, Michael J.
Murakami, Satoshi
van Veen, Hendrik W.
author_sort Agboh, Kelvin
collection PubMed
description LmrA is a bacterial ATP-binding cassette (ABC) multidrug exporter that uses metabolic energy to transport ions, cytotoxic drugs, and lipids. Voltage clamping in a Port-a-Patch was used to monitor electrical currents associated with the transport of monovalent cationic HEPES(+) by single-LmrA transporters and ensembles of transporters. In these experiments, one proton and one chloride ion are effluxed together with each HEPES(+) ion out of the inner compartment, whereas two sodium ions are transported into this compartment. Consequently, the sodium-motive force (interior negative and low) can drive this electrogenic ion exchange mechanism in cells under physiological conditions. The same mechanism is also relevant for the efflux of monovalent cationic ethidium, a typical multidrug transporter substrate. Studies in the presence of Mg-ATP (adenosine 5′-triphosphate) show that ion-coupled HEPES(+) transport is associated with ATP-bound LmrA, whereas ion-coupled ethidium transport requires ATP binding and hydrolysis. HEPES(+) is highly soluble in a water-based environment, whereas ethidium has a strong preference for residence in the water-repelling plasma membrane. We conclude that the mechanism of the ABC transporter LmrA is fundamentally related to that of an ion antiporter that uses extra steps (ATP binding and hydrolysis) to retrieve and transport membrane-soluble substrates from the phospholipid bilayer.
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spelling pubmed-61550542018-09-25 Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force Agboh, Kelvin Lau, Calvin H. F. Khoo, Yvonne S. K. Singh, Himansha Raturi, Sagar Nair, Asha V. Howard, Julie Chiapello, Marco Feret, Renata Deery, Michael J. Murakami, Satoshi van Veen, Hendrik W. Sci Adv Research Articles LmrA is a bacterial ATP-binding cassette (ABC) multidrug exporter that uses metabolic energy to transport ions, cytotoxic drugs, and lipids. Voltage clamping in a Port-a-Patch was used to monitor electrical currents associated with the transport of monovalent cationic HEPES(+) by single-LmrA transporters and ensembles of transporters. In these experiments, one proton and one chloride ion are effluxed together with each HEPES(+) ion out of the inner compartment, whereas two sodium ions are transported into this compartment. Consequently, the sodium-motive force (interior negative and low) can drive this electrogenic ion exchange mechanism in cells under physiological conditions. The same mechanism is also relevant for the efflux of monovalent cationic ethidium, a typical multidrug transporter substrate. Studies in the presence of Mg-ATP (adenosine 5′-triphosphate) show that ion-coupled HEPES(+) transport is associated with ATP-bound LmrA, whereas ion-coupled ethidium transport requires ATP binding and hydrolysis. HEPES(+) is highly soluble in a water-based environment, whereas ethidium has a strong preference for residence in the water-repelling plasma membrane. We conclude that the mechanism of the ABC transporter LmrA is fundamentally related to that of an ion antiporter that uses extra steps (ATP binding and hydrolysis) to retrieve and transport membrane-soluble substrates from the phospholipid bilayer. American Association for the Advancement of Science 2018-09-19 /pmc/articles/PMC6155054/ /pubmed/30255140 http://dx.doi.org/10.1126/sciadv.aas9365 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Agboh, Kelvin
Lau, Calvin H. F.
Khoo, Yvonne S. K.
Singh, Himansha
Raturi, Sagar
Nair, Asha V.
Howard, Julie
Chiapello, Marco
Feret, Renata
Deery, Michael J.
Murakami, Satoshi
van Veen, Hendrik W.
Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title_full Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title_fullStr Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title_full_unstemmed Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title_short Powering the ABC multidrug exporter LmrA: How nucleotides embrace the ion-motive force
title_sort powering the abc multidrug exporter lmra: how nucleotides embrace the ion-motive force
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155054/
https://www.ncbi.nlm.nih.gov/pubmed/30255140
http://dx.doi.org/10.1126/sciadv.aas9365
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