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-Structure paper
| タイトル | Molecular basis for multidrug efflux by an anaerobic-associated RND transporter. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 10601, Year 2025 |
| 掲載日 | 2025年12月3日 |
著者 | Ryan Lawrence / Mohd Athar / Muhammad R Uddin / Christopher Adams / Joana S Sousa / Oliver Durrant / Sophie Lellman / Lucy Sutton / C William Keevil / Nisha Patel / Christine E Prosser / David McMillan / Helen I Zgurskaya / Attilio V Vargiu / Zainab Ahdash / Eamonn Reading / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:41339309 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.2 - 3.56 Å |
| 構造データ | EMDB-53281, PDB-9qpr: EMDB-53282, PDB-9qps: EMDB-53283, PDB-9qpt: |
| 化合物 | ![]() ChemComp-PTY: ![]() ChemComp-D12: ![]() ChemComp-RHQ: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / multidrug / pump / anaerobic / lipid |
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