Ancestral Reconstruction Approach to Acetylcholine Receptor Structure and Function.
Structure
; 25(8): 1295-1302.e3, 2017 08 01.
Article
em En
| MEDLINE
| ID: mdl-28689969
ABSTRACT
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, ß, δ, and É). Here we reconstruct the amino acid sequence of a ß subunit ancestor shared by humans and cartilaginous fishes (i.e., Torpedo). Then, by resurrecting this ancestral ß subunit and co-expressing it with human α, δ, and É 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.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Colinérgicos
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Homologia de Sequência de Aminoácidos
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Proteínas de Peixes
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article