气候变化领域集成服务门户(CCPortal): Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors

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DOI	10.1073/pnas.2007511118
	Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors
	Iacobucci G.J.; Wen H.; Helou M.; Liu B.; Zheng W.; Popescu G.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	NMDA receptors are excitatory channels with critical functions in the physiology of central synapses. Their activation reaction proceeds as a series of kinetically distinguishable, reversible steps, whose structural bases are currently under investigation. Very likely, the earliest steps include glutamate binding to glycine-bound receptors and subsequent constriction of the ligand-binding domain. Later, three short linkers transduce this movement to open the gate by mechanical pulling on transmembrane helices. Here, we used molecular and kinetic simulations and double-mutant cycle analyses to show that a direct chemical interaction between GluN1-I642 (on M3 helix) and GluN2A-L550 (on L1-M1 linker) stabilizes receptors after they have opened and thus represents one of the structural changes that occur late in the activation reaction. This native interaction extends the current decay, and its absence causes deficits in charge transfer by GluN1-I642L, a pathogenic human variant. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Energy landscape; Mutant cycle analysis; NMDA receptor; Single molecule; Targeted molecular dynamics
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/181037
作者单位	Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY 14203, United States; Department of Physics, College of Arts and Sciences, University at Buffalo, SUNY, Buffalo, NY 14260, United States
推荐引用方式 GB/T 7714	Iacobucci G.J.,Wen H.,Helou M.,et al. Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors[J],2021,118(2).
APA	Iacobucci G.J.,Wen H.,Helou M.,Liu B.,Zheng W.,&Popescu G.K..(2021).Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Iacobucci G.J.,et al."Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).