Acetylcholine receptors (AChRs) are members of a superfamily of proteins called pentameric ligand-gated ion channels, which are found in almost all forms of life and thus have a rich evolutionary history. Muscle-type AChRs are heteropentameric complexes assembled from four related subunits (α, β, δ, and ɛ). Here we reconstruct the amino acid sequence of a β subunit ancestor shared by humans and cartilaginous fishes (i.e., Torpedo). Then, by resurrecting this ancestral β subunit and co-expressing it with human α, δ, and ɛ subunits, we show that despite 132 substitutions, the ancestral subunit is capable of forming human/ancestral hybrid AChRs. Whole-cell currents demonstrate that the agonist acetylcholine has reduced potency for hybrid receptors, while single-channel recordings reveal that hybrid receptors display reduced conductance and open probability. Our results outline a promising strategy for studies of AChR evolution aimed at identifying the amino acid origins of AChR structure and function.
Pubmed ID: 28689969 RIS Download
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Web-based software used for the selection of best-fit models of protein evolution.
View all literature mentionsPackage of programs for phylogenetic analyses of DNA or protein sequences using maximum likelihood. PAML estimates parameters and tests hypotheses to study the evolutionary process from a phylogenetic tree.
View all literature mentionsWeb phylogeny server based on the maximum-likelihood principle.
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View all literature mentionsCell line BOSC-23 is a Transformed cell line with a species of origin Homo sapiens (Human)
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