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Flipping and other astonishing transporter dance moves in fungal drug resistance.

cam.issuedOnline2022-04-22
dc.contributor.authorRaschka, Stefanie L
dc.contributor.authorHarris, Andrzej
dc.contributor.authorLuisi, Ben F
dc.contributor.authorSchmitt, Lutz
dc.contributor.orcidHarris, Andrzej [0000-0003-4885-7401]
dc.contributor.orcidLuisi, Ben F [0000-0003-1144-9877]
dc.contributor.orcidSchmitt, Lutz [0000-0002-1167-9819]
dc.date.accessioned2022-06-29T19:45:16Z
dc.date.available2022-06-29T19:45:16Z
dc.date.issued2022-07
dc.date.submitted2022-02-13
dc.date.updated2022-06-29T19:45:16Z
dc.description.abstractIn all domains of life, transmembrane proteins from the ATP-binding cassette (ABC) transporter family drive the translocation of diverse substances across lipid bilayers. In pathogenic fungi, the ABC transporters of the pleiotropic drug resistance (PDR) subfamily confer antibiotic resistance and so are of interest as therapeutic targets. They also drive the quest for understanding how ABC transporters can generally accommodate such a wide range of substrates. The Pdr5 transporter from baker's yeast is representative of the PDR group and, ever since its discovery more than 30 years ago, has been the subject of extensive functional analyses. A new perspective of these studies has been recently provided in the framework of the first electron cryo-microscopy structures of Pdr5, as well as emergent applications of machine learning in the field. Taken together, the old and the new developments have been used to propose a mechanism for the transport process in PDR proteins. This mechanism involves a "flippase" step that moves the substrates from one leaflet of the bilayer to the other, as a central element of cellular efflux.
dc.identifier.doi10.17863/CAM.85913
dc.identifier.eissn1521-1878
dc.identifier.issn0265-9247
dc.identifier.otherbies202200035
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338500
dc.languageen
dc.language.isoeng
dc.publisherWiley
dc.publisher.urlhttp://dx.doi.org/10.1002/bies.202200035
dc.subjectABC transporter
dc.subjectATPase activity
dc.subjectfungal drug resistance
dc.subjectsingle particle cryo EM
dc.subjectATP-Binding Cassette Transporters
dc.subjectDancing
dc.subjectDrug Resistance
dc.subjectSaccharomyces cerevisiae
dc.subjectSaccharomyces cerevisiae Proteins
dc.titleFlipping and other astonishing transporter dance moves in fungal drug resistance.
dc.typeArticle
dcterms.dateAccepted2022-04-12
prism.issueIdentifier7
prism.publicationNameBioessays
prism.volume44
pubs.funder-project-idEuropean Research Council (742210)
pubs.funder-project-idWellcome Trust (200873/Z/16/Z)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1002/bies.202200035

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