9FDP

Single particle cryo-EM structure of the AcrB V612W monomer in the O state

9FDP の概要

• エントリーDOI: 10.2210/pdb9fdp/pdb
• EMDBエントリー: 50331
• 分子名称: Multidrug efflux pump subunit AcrB (1 entity in total)
• 機能のキーワード: drug efflux, rnd transporter, transport protein
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 114823.37

構造登録者

Lazarova, M.,Boernsen, C.,Frangakis, A.,Pos, K.M. (登録日: 2024-05-17, 公開日: 2025-05-28, 最終更新日: 2026-01-07)

主引用文献

Lazarova, M.,Eicher, T.,Bornsen, C.,Zeng, H.,Athar, M.,Okada, U.,Yamashita, E.,Spannaus, I.M.,Borgosch, M.,Cha, H.J.,Vargiu, A.V.,Murakami, S.,Diederichs, K.,Frangakis, A.S.,Pos, K.M.
Conformational plasticity across phylogenetic clusters of RND multidrug efflux pumps and its impact on substrate specificity.
Nat Commun, 16:11649-11649, 2025

PubMed Abstract: Antibiotic efflux plays a key role for the multidrug resistance in Gram-negative bacteria. Multidrug efflux pumps of the resistance nodulation and cell division (RND) superfamily function as part of cell envelope spanning systems and provide resistance to diverse antibiotics. Here, we identify two phylogenetic clusters of RND proteins with conserved binding pocket residues and show that the transfer of a single conserved residue between both clusters affects the resistance phenotype not only due to changes in the physicochemical properties of the binding pocket, but also due to an altered equilibrium between the conformational states of the transport cycle. We demonstrate, using single-particle cryo-electron microscopy, that AcrB and OqxB, which represent both clusters, adopt fundamentally different apo states, implying distinct mechanisms for initial substrate binding. The observed conformational plasticity appears phylogenetically conserved and likely plays a role in the diversification of the resistance phenotype among homologous RND pumps.

PubMed: 41298458
DOI: 10.1038/s41467-025-66751-3

実験手法

ELECTRON MICROSCOPY (3.3 Å)