Optimized tight binding between the S1 segment and KCNE3 is required for the constitutively open nature of the KCNQ1-KCNE3 channel complex

  1. Go Kasuya  Is a corresponding author
  2. Koichi Nakajo  Is a corresponding author
  1. Jichi Medical Univesity, Japan

Abstract

Tetrameric voltage-gated K+ channels have four identical voltage sensor domains, and they regulate channel gating. KCNQ1 (Kv7.1) is a voltage-gated K+ channel, and its auxiliary subunit KCNE proteins dramatically regulate its gating. For example, KCNE3 makes KCNQ1 a constitutively open channel at physiological voltages by affecting the voltage sensor movement. However, how KCNE proteins regulate the voltage sensor domain is largely unknown. In this study, by utilizing the KCNQ1-KCNE3-calmodulin complex structure, we thoroughly surveyed amino acid residues on KCNE3 and the S1 segment of the KCNQ1 voltage sensor facing each other. By changing the side-chain bulkiness of these interacting amino acid residues (volume scanning), we found that the distance between the S1 segment and KCNE3 is elaborately optimized to achieve the constitutive activity. In addition, we identified two pairs of KCNQ1 and KCNE3 mutants that partially restored constitutive activity by co-expression. Our work suggests that tight binding of the S1 segment and KCNE3 is crucial for controlling the voltage sensor domains.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. Go Kasuya

    Department of Physiology, Jichi Medical Univesity, Shimotsuke, Japan
    For correspondence
    gokasuya@jichi.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1756-5764
  2. Koichi Nakajo

    Department of Physiology, Jichi Medical Univesity, Shimotsuke, Japan
    For correspondence
    knakajo@jichi.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0766-7281

Funding

Japan Society for the Promotion of Science (19K23833)

  • Go Kasuya

Japan Society for the Promotion of Science (20H03200)

  • Go Kasuya

Japan Society for the Promotion of Science (17K08552)

  • Koichi Nakajo

Japan Society for the Promotion of Science (21K06786)

  • Koichi Nakajo

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

Reviewing Editor

  1. Jon T Sack, University of California Davis School of Medicine, United States

Ethics

Animal experimentation: All experiments were approved by the Animal Care Committee of Jichi Medical University(Japan) under protocol no. 18027-03 and were performed according to guidelines.

Version history

  1. Preprint posted: April 6, 2021 (view preprint)
  2. Received: July 29, 2022
  3. Accepted: November 3, 2022
  4. Accepted Manuscript published: November 4, 2022 (version 1)
  5. Version of Record published: November 17, 2022 (version 2)

Copyright

© 2022, Kasuya & Nakajo

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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  1. Go Kasuya
  2. Koichi Nakajo
(2022)
Optimized tight binding between the S1 segment and KCNE3 is required for the constitutively open nature of the KCNQ1-KCNE3 channel complex
eLife 11:e81683.
https://doi.org/10.7554/eLife.81683

Share this article

https://doi.org/10.7554/eLife.81683

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