9qpr
From Proteopedia
Single particle cryo-EM structure of the multidrug efflux pump MdtF from Escherichia coli
Structural highlights
FunctionMDTF_ECOLI Part of the tripartite efflux system MdtEF-TolC, which confers resistance to compounds such as rhodamine 6G, erythromycin, doxorubicin, ethidium bromide, TPP, SDS, deoxycholate, crystal violet and benzalkonium.[1] Publication Abstract from PubMedBacteria 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. Molecular basis for multidrug efflux by an anaerobic RND transporter.,Lawrence R, Athar M, Uddin MR, Adams C, Sousa JS, Durrant O, Lellman S, Sutton L, Keevil CW, Patel N, Prosser C, McMillan D, Zgurskaya HI, Vargiu AV, Ahdash Z, Reading E bioRxiv [Preprint]. 2025 Apr 5:2025.04.04.646765. doi: 10.1101/2025.04.04.646765. PMID:40236129[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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