9QPR

Single particle cryo-EM structure of the multidrug efflux pump MdtF from Escherichia coli

9QPR の概要

• エントリーDOI: 10.2210/pdb9qpr/pdb
• EMDBエントリー: 53281
• 分子名称: Multidrug resistance protein MdtF, PHOSPHATIDYLETHANOLAMINE, DODECANE (3 entities in total)
• 機能のキーワード: multidrug, pump, anaerobic, lipid, membrane protein
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 357886.77

構造登録者

Lawrence, R.,Adams, C.,Sousa, J.S.,Ahdash, Z.,Reading, E. (登録日: 2025-03-28, 公開日: 2025-05-14)

主引用文献

Lawrence, R.,Athar, M.,Uddin, M.R.,Adams, C.,Sousa, J.S.,Durrant, O.,Lellman, S.,Sutton, L.,Keevil, C.W.,Patel, N.,Prosser, C.,McMillan, D.,Zgurskaya, H.I.,Vargiu, A.V.,Ahdash, Z.,Reading, E.
Molecular basis for multidrug efflux by an anaerobic RND transporter.
Biorxiv, 2025

PubMed Abstract: Bacteria can resist antibiotics and toxic substances within demanding ecological settings, such as low oxygen, extreme acid, and during nutrient starvation. MdtEF, a proton motive force-driven efflux pump from the resistance-nodulation-cell division (RND) superfamily, is upregulated in these conditions but its molecular mechanism is unknown. Here, we report cryo-electron microscopy structures of Escherichia coli multidrug transporter MdtF within native-lipid nanodiscs, including a single-point mutant with an altered multidrug phenotype and associated substrate-bound form. We reveal that drug binding domain and channel conformational plasticity likely governs promiscuous substrate specificity, analogous to its closely related, constitutively expressed counterpart, AcrB. Whereas we discover distinct transmembrane state transitions within MdtF, which create a more engaged proton relay network, altered drug transport allostery and an acid-responsive increase in efflux efficiency. Physiologically, this provides means of xenobiotic and metabolite disposal within remodelled cell membranes that presage encounters with acid stresses, as endured in the gastrointestinal tract.

PubMed: 40236129
DOI: 10.1101/2025.04.04.646765

実験手法

ELECTRON MICROSCOPY (3.56 Å)