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Structure and function of H+/K+ pump mutants reveal Na+/K+ pump mechanisms

Author

Listed:
  • Victoria C. Young

    (Texas Tech University Health Sciences Center)

  • Hanayo Nakanishi

    (Nagoya University)

  • Dylan J. Meyer

    (Texas Tech University Health Sciences Center)

  • Tomohiro Nishizawa

    (Yokohama City University, Tsurumi)

  • Atsunori Oshima

    (Nagoya University
    Nagoya University
    Nagoya University)

  • Pablo Artigas

    (Texas Tech University Health Sciences Center)

  • Kazuhiro Abe

    (Nagoya University
    Nagoya University)

Abstract

Ion-transport mechanisms evolve by changing ion-selectivity, such as switching from Na+ to H+ selectivity in secondary-active transporters or P-type-ATPases. Here we study primary-active transport via P-type ATPases using functional and structural analyses to demonstrate that four simultaneous residue substitutions transform the non-gastric H+/K+ pump, a strict H+-dependent electroneutral P-type ATPase, into a bona fide Na+-dependent electrogenic Na+/K+ pump. Conversion of a H+-dependent primary-active transporter into a Na+-dependent one provides a prototype for similar studies of ion-transport proteins. Moreover, we solve the structures of the wild-type non-gastric H+/K+ pump, a suitable drug target to treat cystic fibrosis, and of its Na+/K+ pump-mimicking mutant in two major conformations, providing insight on how Na+ binding drives a concerted mechanism leading to Na+/K+ pump phosphorylation.

Suggested Citation

  • Victoria C. Young & Hanayo Nakanishi & Dylan J. Meyer & Tomohiro Nishizawa & Atsunori Oshima & Pablo Artigas & Kazuhiro Abe, 2022. "Structure and function of H+/K+ pump mutants reveal Na+/K+ pump mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32793-0
    DOI: 10.1038/s41467-022-32793-0
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    References listed on IDEAS

    as
    1. Kazuhiro Abe & Kenta Yamamoto & Katsumasa Irie & Tomohiro Nishizawa & Atsunori Oshima, 2021. "Gastric proton pump with two occluded K+ engineered with sodium pump-mimetic mutations," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Takehiro Shinoda & Haruo Ogawa & Flemming Cornelius & Chikashi Toyoshima, 2009. "Crystal structure of the sodium–potassium pump at 2.4 Å resolution," Nature, Nature, vol. 459(7245), pages 446-450, May.
    3. J. Preben Morth & Bjørn P. Pedersen & Mads S. Toustrup-Jensen & Thomas L.-M. Sørensen & Janne Petersen & Jens Peter Andersen & Bente Vilsen & Poul Nissen, 2007. "Crystal structure of the sodium–potassium pump," Nature, Nature, vol. 450(7172), pages 1043-1049, December.
    4. Abdul S. Ethayathulla & Mohammad S. Yousef & Anowarul Amin & Gérard Leblanc & H. Ronald Kaback & Lan Guan, 2014. "Structure-based mechanism for Na+/melibiose symport by MelB," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    5. Chikashi Toyoshima & Hiromi Nomura, 2002. "Structural changes in the calcium pump accompanying the dissociation of calcium," Nature, Nature, vol. 418(6898), pages 605-611, August.
    6. Harini Krishnamurthy & Chayne L. Piscitelli & Eric Gouaux, 2009. "Unlocking the molecular secrets of sodium-coupled transporters," Nature, Nature, vol. 459(7245), pages 347-355, May.
    7. Kazuhiro Abe & Katsumasa Irie & Hanayo Nakanishi & Hiroshi Suzuki & Yoshinori Fujiyoshi, 2018. "Crystal structures of the gastric proton pump," Nature, Nature, vol. 556(7700), pages 214-218, April.
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