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Substrate-bound structure of the E. coli multidrug resistance transporter MdfA.

ABSTRACT: Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes at resolutions up to 2.0 Å, all in the inward-facing conformation. The substrate-binding site sits proximal to the conserved acidic residue, D34. Our mutagenesis studies support the structural observations of the substrate-binding mode and the notion that D34 responds to substrate binding by adjusting its protonation status. Taken together, our data unveil the substrate-binding mode of MFS antiporters and suggest a mechanism of transport via this group of transporters.

SUBMITTER: Heng J

PROVIDER: S-EPMC4559816 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Substrate-bound structure of the E. coli multidrug resistance transporter MdfA.

Heng Jie J Zhao Yan Y Liu Ming M Liu Yue Y Fan Junping J Wang Xianping X Zhao Yongfang Y Zhang Xuejun C XC

Cell research 20150804 9

Multidrug resistance is a serious threat to public health. Proton motive force-driven antiporters from the major facilitator superfamily (MFS) constitute a major group of multidrug-resistance transporters. Currently, no reports on crystal structures of MFS antiporters in complex with their substrates exist. The E. coli MdfA transporter is a well-studied model system for biochemical analyses of multidrug-resistance MFS antiporters. Here, we report three crystal structures of MdfA-ligand complexes ...[more]

PMID: 26238402

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