Abstract

Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from two α-subunits, and one each of the β-, d-, and e-subunits. To form functional channels, the subunits must assemble with one another in a precise stoichiometry and arrangement. Despite being different, the four subunits share a common ancestor that is presumed to have formed homopentamers. The extent to which the properties of the modern-day receptor result from its subunit complexity is unknown. Here we discover that a reconstructed ancestral muscle-type β-subunit can form homopentameric ion channels. These homopentamers open spontaneously and display single-channel hallmarks of muscle-type acetylcholine receptor activity. Our findings attest to the homopentameric origin of the muscle-type acetylcholine receptor, and demonstrate that signature features of its function are both independent of agonist and do not necessitate the complex heteropentameric architecture of the modern-day protein.

Data availability

All data generated and analysed during this study are included in the manuscript and as source data

Article and author information

Author details

  1. Christian JG Tessier

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. R Michel Sturgeon

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Johnathon R Emlaw

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7255-182X
  4. Gregory D McCluskey

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. F Javier Pérez-Areales

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9525-9346
  6. Corrie JB daCosta

    Center for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada
    For correspondence
    cdacosta@uottawa.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9546-5331

Funding

Natural Sciences and Engineering Research Council of Canada (Discovery Grant,RGPIN-2016-04801)

  • Corrie JB daCosta

Canadian Institutes of Health Research (Project Grant,377068)

  • Corrie JB daCosta

Ontario Council on Graduate Studies, Council of Ontario Universities (Graduate Scholarship)

  • Christian JG Tessier

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

Reviewing Editor

  1. Stephan A Pless, University of Copenhagen, Denmark

Version history

  1. Received: December 18, 2021
  2. Preprint posted: January 13, 2022 (view preprint)
  3. Accepted: June 21, 2022
  4. Accepted Manuscript published: July 4, 2022 (version 1)
  5. Version of Record published: August 10, 2022 (version 2)

Copyright

© 2022, Tessier 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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  1. Christian JG Tessier
  2. R Michel Sturgeon
  3. Johnathon R Emlaw
  4. Gregory D McCluskey
  5. F Javier Pérez-Areales
  6. Corrie JB daCosta
(2022)
Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously
eLife 11:e76504.
https://doi.org/10.7554/eLife.76504

Share this article

https://doi.org/10.7554/eLife.76504

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