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Cryo-EM structures of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae

Author

Listed:
  • Jun-ichi Kishikawa

    (Osaka University)

  • Moe Ishikawa

    (Kyoto University)

  • Takahiro Masuya

    (Kyoto University)

  • Masatoshi Murai

    (Kyoto University)

  • Yuki Kitazumi

    (Kyoto University)

  • Nicole L. Butler

    (Rensselaer Polytechnic Institute)

  • Takayuki Kato

    (Osaka University)

  • Blanca Barquera

    (Rensselaer Polytechnic Institute
    Rensselaer Polytechnic Institute
    Rensselaer Polytechinic Institute)

  • Hideto Miyoshi

    (Kyoto University)

Abstract

The Na+-pumping NADH-ubiquinone oxidoreductase (Na+-NQR) couples electron transfer from NADH to ubiquinone with Na+-pumping, generating an electrochemical Na+ gradient that is essential for energy-consuming reactions in bacteria. Since Na+-NQR is exclusively found in prokaryotes, it is a promising target for highly selective antibiotics. However, the molecular mechanism of inhibition is not well-understood for lack of the atomic structural information about an inhibitor-bound state. Here we present cryo-electron microscopy structures of Na+-NQR from Vibrio cholerae with or without a bound inhibitor at 2.5- to 3.1-Å resolution. The structures reveal the arrangement of all six redox cofactors including a herein identified 2Fe-2S cluster located between the NqrD and NqrE subunits. A large part of the hydrophilic NqrF is barely visible in the density map, suggesting a high degree of flexibility. This flexibility may be responsible to reducing the long distance between the 2Fe-2S centers in NqrF and NqrD/E. Two different types of specific inhibitors bind to the N-terminal region of NqrB, which is disordered in the absence of inhibitors. The present study provides a foundation for understanding the function of Na+-NQR and the binding manner of specific inhibitors.

Suggested Citation

  • Jun-ichi Kishikawa & Moe Ishikawa & Takahiro Masuya & Masatoshi Murai & Yuki Kitazumi & Nicole L. Butler & Takayuki Kato & Blanca Barquera & Hideto Miyoshi, 2022. "Cryo-EM structures of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31718-1
    DOI: 10.1038/s41467-022-31718-1
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    References listed on IDEAS

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    1. Christopher C. Page & Christopher C. Moser & Xiaoxi Chen & P. Leslie Dutton, 1999. "Natural engineering principles of electron tunnelling in biological oxidation–reduction," Nature, Nature, vol. 402(6757), pages 47-52, November.
    2. Julia Steuber & Georg Vohl & Marco S. Casutt & Thomas Vorburger & Kay Diederichs & Günter Fritz, 2014. "Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase," Nature, Nature, vol. 516(7529), pages 62-67, December.
    3. Tomonori Tamura & Tsuyoshi Ueda & Taiki Goto & Taku Tsukidate & Yonatan Shapira & Yuki Nishikawa & Alma Fujisawa & Itaru Hamachi, 2018. "Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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