Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously
- University of Ottawa, Canada
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.
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All data generated and analysed during this study are included in the manuscript and as source data
Article and author information
Author details
F Javier Pérez-Areales
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.
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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Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously
eLife 11:e76504.
https://doi.org/10.7554/eLife.76504
