7P04

Cryo-EM structure of Pdr5 from Saccharomyces cerevisiae in inward-facing conformation with ADP/ATP

Summary for 7P04

• Entry DOI: 10.2210/pdb7p04/pdb
• EMDB information: 13143
• Descriptor: Pleiotropic ABC efflux transporter of multiple drugs, ADENOSINE-5'-TRIPHOSPHATE, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: abc transporter, antibiotic resistance, membrane protein, fungal infection, transport protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 171551.63

Authors

Szewczak-Harris, A.,Wagner, M.,Du, D.,Schmitt, L.,Luisi, B.F. (deposition date: 2021-06-29, release date: 2021-11-10, Last modification date: 2024-11-13)

Primary citation

Harris, A.,Wagner, M.,Du, D.,Raschka, S.,Nentwig, L.M.,Gohlke, H.,Smits, S.H.J.,Luisi, B.F.,Schmitt, L.
Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5.
Nat Commun, 12:5254-5254, 2021

PubMed Abstract: Pdr5, a member of the extensive ABC transporter superfamily, is representative of a clinically relevant subgroup involved in pleiotropic drug resistance. Pdr5 and its homologues drive drug efflux through uncoupled hydrolysis of nucleotides, enabling organisms such as baker's yeast and pathogenic fungi to survive in the presence of chemically diverse antifungal agents. Here, we present the molecular structure of Pdr5 solved with single particle cryo-EM, revealing details of an ATP-driven conformational cycle, which mechanically drives drug translocation through an amphipathic channel, and a clamping switch within a conserved linker loop that acts as a nucleotide sensor. One half of the transporter remains nearly invariant throughout the cycle, while its partner undergoes changes that are transmitted across inter-domain interfaces to support a peristaltic motion of the pumped molecule. The efflux model proposed here rationalises the pleiotropic impact of Pdr5 and opens new avenues for the development of effective antifungal compounds.

PubMed: 34489436
DOI: 10.1038/s41467-021-25574-8

Experimental method

ELECTRON MICROSCOPY (2.85 Å)