气候变化领域集成服务门户(CCPortal): A single historical substitution drives an increase in acetylcholine receptor complexity

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DOI	10.1073/pnas.2018731118
	A single historical substitution drives an increase in acetylcholine receptor complexity
	Emlaw J.R.; Tessier C.J.G.; McCluskey G.D.; McNulty M.S.; Sheikh Y.; Burkett K.M.; Musgaard M.; daCosta C.J.B.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	Human adult muscle-type acetylcholine receptors are heteropentameric ion channels formed from four different, but evolutionarily related, subunits. These subunits assemble with a precise stoichiometry and arrangement such that two chemically distinct agonist-binding sites are formed between specific subunit pairs. How this subunit complexity evolved and became entrenched is unclear. Here we show that a single historical amino acid substitution is able to constrain the subunit stoichiometry of functional acetylcholine receptors. Using a combination of ancestral sequence reconstruction, single-channel electrophysiology, and concatenated subunits, we reveal that an ancestral β-subunit can not only replace the extant β-subunit but can also supplant the neighboring δ-subunit. By forward evolving the ancestral β-subunit with a single amino acid substitution, we restore the requirement for a δ-subunit for functional channels. These findings reveal that a single historical substitution necessitates an increase in acetylcholine receptor complexity and, more generally, that simple stepwise mutations can drive subunit entrenchment in this model heteromeric protein. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Nicotinic acetylcholine receptor \| patch clamping \| electrical fingerprinting \| evolutionary biochemistry \| ancestral reconstruction
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180634
作者单位	Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Department of Mathematics and Statistics, University of Ottawa, Ottawa, ON K1N 6N5, Canada
推荐引用方式 GB/T 7714	Emlaw J.R.,Tessier C.J.G.,McCluskey G.D.,et al. A single historical substitution drives an increase in acetylcholine receptor complexity[J],2021,118(7).
APA	Emlaw J.R..,Tessier C.J.G..,McCluskey G.D..,McNulty M.S..,Sheikh Y..,...&daCosta C.J.B..(2021).A single historical substitution drives an increase in acetylcholine receptor complexity.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Emlaw J.R.,et al."A single historical substitution drives an increase in acetylcholine receptor complexity".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).