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

Autor:	Tessier CJG; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada., Sturgeon RM; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada., Emlaw JR; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada., McCluskey GD; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada., Pérez-Areales FJ; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada., daCosta CJB; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Canada.; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, Canada.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Jul 04; Vol. 11. Date of Electronic Publication: 2022 Jul 04.
DOI:	10.7554/eLife.76504
Abstrakt:	Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from two α-subunits, and one each of the β-, δ-, and ε-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. Competing Interests: CT, RS, JE, GM, FP, Cd No competing interests declared (© 2022, Tessier et al.)
Databáze:	MEDLINE
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