7P06

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

7P06 の概要

• エントリーDOI: 10.2210/pdb7p06/pdb
• EMDBエントリー: 13145
• 分子名称: Pleiotropic ABC efflux transporter of multiple drugs, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: abc transporter, antibiotic resistance, membrane protein, fungal infection, transport protein
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 171692.89

構造登録者

Szewczak-Harris, A.,Wagner, M.,Du, D.,Schmitt, L.,Luisi, B.F. (登録日: 2021-06-29, 公開日: 2021-11-10, 最終更新日: 2024-10-16)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.77 Å)