9QPS

Single particle cryo-EM structure of MdtF V610F

9QPS の概要

• エントリーDOI: 10.2210/pdb9qps/pdb
• EMDBエントリー: 53282
• 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: 359446.24

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, 最終更新日: 2026-04-22)

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.E.,McMillan, D.,Zgurskaya, H.I.,Vargiu, A.V.,Ahdash, Z.,Reading, E.
Molecular basis for multidrug efflux by an anaerobic-associated RND transporter.
Nat Commun, 16:10601-10601, 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. Drug binding domain and channel conformational plasticity likely governs substrate polyspecificity, analogous to 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. Our findings provide mechanistic insights necessary to understand bacterial xenobiotic and toxin removal by MdtF and its role within nutrient-depleted and acid stress settings, as endured in the gastrointestinal tract.

PubMed: 41339309
DOI: 10.1038/s41467-025-65565-7

実験手法

ELECTRON MICROSCOPY (3.28 Å)