Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously
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
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
- Stephan A Pless, University of Copenhagen, Denmark
Publication history
- Received: December 18, 2021
- Preprint posted: January 13, 2022 (view preprint)
- Accepted: June 21, 2022
- Accepted Manuscript published: July 4, 2022 (version 1)
- 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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Further reading
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