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dc.contributor.authorGuo, Dawei
dc.contributor.authorSingh, Himansha
dc.contributor.authorShimoyama, Atsushi
dc.contributor.authorGuffick, Charlotte
dc.contributor.authorTang, Yakun
dc.contributor.authorRowe, Sam M
dc.contributor.authorNoel, Timothy
dc.contributor.authorSpring, David R
dc.contributor.authorFukase, Koichi
dc.contributor.authorvan Veen, Hendrik W
dc.date.accessioned2022-01-04T11:58:34Z
dc.date.available2022-01-04T11:58:34Z
dc.date.issued2021-12-09
dc.date.submitted2021-05-09
dc.identifier.issn2399-3642
dc.identifier.others42003-021-02902-8
dc.identifier.other2902
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331846
dc.descriptionFunder: China Scholarship Council (CSC); doi: https://doi.org/10.13039/501100004543
dc.descriptionFunder: Cambridge Commonwealth Trust; doi: https://doi.org/10.13039/501100003342
dc.description.abstractThe 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.
dc.description.sponsorshipThis 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.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/45/287/1192
dc.subject/631/45/173
dc.subject/631/326/22/1434
dc.subject/82/83
dc.subject/82/80
dc.subject/96/34
dc.subject/82/29
dc.subject/96/44
dc.subjectarticle
dc.titleEnergetics of lipid transport by the ABC transporter MsbA is lipid dependent.
dc.typeArticle
dc.date.updated2022-01-04T11:58:33Z
prism.issueIdentifier1
prism.publicationNameCommun Biol
prism.volume4
dc.identifier.doi10.17863/CAM.79296
dcterms.dateAccepted2021-11-18
rioxxterms.versionofrecord10.1038/s42003-021-02902-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidShimoyama, Atsushi [0000-0003-1910-0450]
dc.contributor.orcidRowe, Sam M [0000-0003-4902-6685]
dc.contributor.orcidSpring, David R [0000-0001-7355-2824]
dc.contributor.orcidvan Veen, Hendrik W [0000-0002-9658-8077]
dc.identifier.eissn2399-3642
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/R00224X/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (2114197)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/K017713/1)
cam.issuedOnline2021-12-09
datacite.issupplementedby.doi10.17863/CAM.75215
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.75215


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