9QPT

Single particle cryo-EM structure of MdtF V610F with bound Rhodamine 6G

Summary for 9QPT

• Entry DOI: 10.2210/pdb9qpt/pdb
• EMDB information: 53283
• Descriptor: Multidrug resistance protein MdtF, DODECANE, PHOSPHATIDYLETHANOLAMINE, ... (4 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: 360794.17

Authors

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

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.,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

Experimental method

ELECTRON MICROSCOPY (3.2 Å)