7p06

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

spinqualitylabelsall models 7p06, resolution 3.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.77Å Ligands: AOV, ATP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5.,Harris A, Wagner M, Du D, Raschka S, Nentwig LM, Gohlke H, Smits SHJ, Luisi BF, Schmitt L Nat Commun. 2021 Sep 6;12(1):5254. doi: 10.1038/s41467-021-25574-8. PMID:34489436 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ABC transporter 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA