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Structural basis for xenobiotic extrusion by eukaryotic MATE transporter

Author

Listed:
  • Hirotake Miyauchi

    (Graduate School of Science, The University of Tokyo)

  • Satomi Moriyama

    (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)

  • Tsukasa Kusakizako

    (Graduate School of Science, The University of Tokyo)

  • Kaoru Kumazaki

    (Graduate School of Science, The University of Tokyo)

  • Takanori Nakane

    (Graduate School of Science, The University of Tokyo)

  • Keitaro Yamashita

    (RIKEN SPring-8 Center, Sayo-gun)

  • Kunio Hirata

    (RIKEN SPring-8 Center, Sayo-gun)

  • Naoshi Dohmae

    (RIKEN Center for Sustainable Resource Science, Wako)

  • Tomohiro Nishizawa

    (Graduate School of Science, The University of Tokyo)

  • Koichi Ito

    (Graduate School of Frontier Sciences, The University of Tokyo)

  • Takaaki Miyaji

    (Okayama University)

  • Yoshinori Moriyama

    (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)

  • Ryuichiro Ishitani

    (Graduate School of Science, The University of Tokyo)

  • Osamu Nureki

    (Graduate School of Science, The University of Tokyo)

Abstract

Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and secondary metabolite transport. Here we report the crystal structure of the eukaryotic MATE transporter from Arabidopsis thaliana, at 2.6 Å resolution. The structure reveals that its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, and their importance is demonstrated by the structure-based mutational analysis. The structural and functional analyses suggest that the transport mechanism involves the structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe. Our findings provide insights into the transport mechanism of eukaryotic MATE transporters, which is important for the improvement of the pharmacokinetics of the clinical drugs.

Suggested Citation

  • Hirotake Miyauchi & Satomi Moriyama & Tsukasa Kusakizako & Kaoru Kumazaki & Takanori Nakane & Keitaro Yamashita & Kunio Hirata & Naoshi Dohmae & Tomohiro Nishizawa & Koichi Ito & Takaaki Miyaji & Yosh, 2017. "Structural basis for xenobiotic extrusion by eukaryotic MATE transporter," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01541-0
    DOI: 10.1038/s41467-017-01541-0
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    Cited by:

    1. Han Ba Bui & Satoshi Watanabe & Norimichi Nomura & Kehong Liu & Tomoko Uemura & Michio Inoue & Akihisa Tsutsumi & Hiroyuki Fujita & Kengo Kinoshita & Yukinari Kato & So Iwata & Masahide Kikkawa & Kenj, 2023. "Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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