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bioRxiv · 10.1101/2022.01.12.475990

Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously

Tessier, C. J. G.·Sturgeon, R. M.·Emlaw, J. R.·McCluskey, G. D.·Perez-Areales, F. J.·daCosta, C. J. B.
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Abstract

Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from two -subunits, and one each of the {beta}-, {delta}-, and {varepsilon}-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 show that a reconstructed ancestral muscle-type {beta}-subunit can form homopentameric ion channels. These homopentamers open spontaneously and display single-channel hallmarks of muscle-type acetylcholine receptor activity. Our findings demonstrate that signature features of muscle-type acetylcholine receptor function are independent of agonist, and do not necessitate the complex heteropentameric architecture of the modern-day receptor.

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Tessier, C. J. G., Sturgeon, R. M., Emlaw, J. R., McCluskey, G. D., Perez-Areales, F. J., daCosta, C. J. B.. 2022-01-13. Ancestral acetylcholine receptor β-subunit forms homopentamers that prime before opening spontaneously. https://doi.org/10.1101/2022.01.12.475990

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