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bioRxiv · 10.1101/2020.06.11.145466

Structural correlates of human muscle nicotinic acetylcholine receptor subunit assembly mediated by δ(+) interface residues

Epstein, M.·Maxwell, S.·Piggot, T. J.·Beeson, D.·Bermudez, I.·Biggin, P. C.
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Abstract

Muscle nicotinic acetylcholine receptors are a class of heteropentameric ligand-gated cation channels with constituent subunits adopting a fixed stoichiometric arrangement. The specific amino acid residues that govern subunit ordering are however, only partially understood. By integrating all-atom molecular dynamics simulations, bioinformatics, two-electrode voltage clamp electrophysiology and 125I--bungarotoxin assays of chimeric nAChR subunits, we identify residues across the extracellular, transmembrane and extended M4 helix of the {delta} subunit that make structural signatures that contribute to intransigent assembly rules. Furthermore, functional differences observed in 2{delta}2{beta} receptors can be rationalized by changes in dynamical behavior that manifest themselves at the agonist binding site.

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Epstein, M., Maxwell, S., Piggot, T. J., Beeson, D., Bermudez, I., Biggin, P. C.. 2020-06-12. Structural correlates of human muscle nicotinic acetylcholine receptor subunit assembly mediated by δ(+) interface residues. https://doi.org/10.1101/2020.06.11.145466

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