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Energetics of lipid transport by the ABC transporter MsbA is lipid dependent.

Published version
Peer-reviewed

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Authors

Guo, Dawei 
Singh, Himansha 
Guffick, Charlotte 
Tang, Yakun 

Abstract

The ABC multidrug exporter MsbA mediates the translocation of lipopolysaccharides and phospholipids across the plasma membrane in Gram-negative bacteria. Although MsbA is structurally well characterised, the energetic requirements of lipid transport remain unknown. Here, we report that, similar to the transport of small-molecule antibiotics and cytotoxic agents, the flopping of physiologically relevant long-acyl-chain 1,2-dioleoyl (C18)-phosphatidylethanolamine in proteoliposomes requires the simultaneous input of ATP binding and hydrolysis and the chemical proton gradient as sources of metabolic energy. In contrast, the flopping of the large hexa-acylated (C12-C14) Lipid-A anchor of lipopolysaccharides is only ATP dependent. This study demonstrates that the energetics of lipid transport by MsbA is lipid dependent. As our mutational analyses indicate lipid and drug transport via the central binding chamber in MsbA, the lipid availability in the membrane can affect the drug transport activity and vice versa.

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Journal Title

Commun Biol

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Journal ISSN

2399-3642
2399-3642

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/R00224X/1)
Biotechnology and Biological Sciences Research Council (2114197)
This research was funded by Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/R00224X/1 (to H.W.V.V). D.G. and Y.T. were funded by China Scholarship Council – Cambridge Trust PhD Scholarships. C.G. was funded by a BBSRC Doctoral Training Partnership (DTP) Targeted PhD studentship (project 2114197). T.N. received a student grant from Christ’s College Cambridge.
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