1. Structural Biology and Molecular Biophysics
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The hydrophobic nature of a novel membrane interface regulates the enzyme activity of a voltage-sensing phosphatase

  1. Akira Kawanabe
  2. Masaki Hashimoto
  3. Manami Nishizawa
  4. Kazuhisa Nishizawa
  5. Hirotaka Narita
  6. Tomoko Yonezawa
  7. Yuka Jinno
  8. Souhei Sakata
  9. Atsushi Nakagawa
  10. Yasushi Okamura  Is a corresponding author
  1. Osaka University, Japan
  2. Teikyo University, Japan
  3. Osaka Medical College, Japan
Research Article
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Cite this article as: eLife 2018;7:e41653 doi: 10.7554/eLife.41653

Abstract

Voltage-sensing phosphatases (VSP) contain a voltage sensor domain (VSD) similar to that of voltage-gated ion channels but lack a pore-gate domain. A VSD in a VSP regulates the cytoplasmic catalytic region (CCR). However, the mechanisms by which the VSD couples to the CCR remain elusive. Here we report a membrane interface (named 'the hydrophobic spine'), which is essential for the coupling of the VSD and CCR. Our molecular dynamics simulations suggest that the hydrophobic spine of Ciona intestinalis VSP (Ci-VSP) provides a hinge-like motion for the CCR through the loose membrane association of the phosphatase domain. Electrophysiological experiments indicate that the voltage-dependent phosphatase activity of Ci-VSP depends on the hydrophobicity and presence of an aromatic ring in the hydrophobic spine. Analysis of conformational changes in the VSD and CCR suggests that the VSP has two states with distinct enzyme activities and that the second transition depends on the hydrophobic spine.

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Author details

  1. Akira Kawanabe

    Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Masaki Hashimoto

    Graduate School of Frontier Biosciences, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Manami Nishizawa

    School of Medical Technology, Teikyo University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Kazuhisa Nishizawa

    School of Medical Technology, Teikyo University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Hirotaka Narita

    Institute for Protein Research, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Tomoko Yonezawa

    Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Yuka Jinno

    Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Souhei Sakata

    Department of Physiology, Division of Life Sciences, Faculty of Medicine, Osaka Medical College, Takatsuki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Atsushi Nakagawa

    Institute for Protein Research, Osaka University, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  10. Yasushi Okamura

    Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Japan
    For correspondence
    yokamura@phys2.med.osaka-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5386-7968

Funding

Core Research for Evolutional Science and Technology (JPMJCR14M3)

  • Atsushi Nakagawa
  • Yasushi Okamura

Ministry of Education, Culture, Sports, Science, and Technology (25253016)

  • Yasushi Okamura

Japan Society for the Promotion of Science (15H05901)

  • Yasushi Okamura

Japan Society for the Promotion of Science (JP15K18516)

  • Akira Kawanabe

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were carried out following the guidelines of the Animal Research Committees of the Graduate School of Medicine of Osaka University.

Reviewing Editor

  1. Baron Chanda, University of Wisconsin-Madison, United States

Publication history

  1. Received: September 1, 2018
  2. Accepted: November 28, 2018
  3. Accepted Manuscript published: November 28, 2018 (version 1)

Copyright

© 2018, Kawanabe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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