Flipping and other astonishing transporter dance moves in fungal drug resistance.
Publication Date
2022-07Journal Title
Bioessays
ISSN
0265-9247
Publisher
Wiley
Volume
44
Issue
7
Language
en
Type
Article
This Version
AO
VoR
Metadata
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Raschka, S. L., Harris, A., Luisi, B., & Schmitt, L. (2022). Flipping and other astonishing transporter dance moves in fungal drug resistance.. Bioessays, 44 (7) https://doi.org/10.1002/bies.202200035
Abstract
In 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.
Keywords
HYPOTHESIS, ABC transporter, ATPase activity, fungal drug resistance, single particle cryo EM
Sponsorship
European Research Council (742210)
Identifiers
bies202200035
External DOI: https://doi.org/10.1002/bies.202200035
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338500
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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