9QPR

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

Summary for 9QPR

• Entry DOI: 10.2210/pdb9qpr/pdb
• EMDB information: 53281
• Descriptor: Multidrug resistance protein MdtF, PHOSPHATIDYLETHANOLAMINE, DODECANE (3 entities in total)
• Functional Keywords: multidrug, pump, anaerobic, lipid, membrane protein
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 3
• Total formula weight: 357886.77

Authors

Lawrence, R.,Adams, C.,Sousa, J.S.,Ahdash, Z.,Reading, E. (deposition date: 2025-03-28, release date: 2025-05-14, Last modification date: 2026-04-22)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.56 Å)