A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation.

A chimeric prokaryotic pentameric ligand-gated channel reveals distinct pathways of activation.
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嵌合原核五聚体配体门控通道揭示了不同的激活途径。

DOI：
10.1085/jgp.201511478
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发表时间：
2015
期刊：
The Journal of general physiology
影响因子：
--
通讯作者：
Chakrapani,Sudha
Chakrapani,Sudha
中科院分区：
--
文献类型：
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作者：
Schmandt,Nicolaus;Velisetty,Phanindra;Chalamalasetti,SreevatsaV;Stein,RichardA;Bonner,Ross;Talley,Lauren;Parker,MarkD;Mchaourab,HassaneS;Yee,VivienC;Lodowski,DavidT;Chakrapani,Sudha

文献摘要

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五聚体配体门通离子通道（plics）介导中枢和外周神经系统的快速突触传递，该家族的脊椎动物成员包括烟碱乙酰胆碱（ACh）受体（nAChRs）、-氨基丁酸受体（GABAARs）、甘氨酸受体（GlyRs）和血清素受体（5HT3Rs）（Sine和Engel, 2006； Thompson等人，2010；Corringer等人，2012；daCosta和Baenziger， 2013）。plgic在与学习和记忆相关的神经元功能中起着关键作用，这些通道的功能障碍是多种神经退行性疾病的基础，包括阿尔茨海默病、帕金森病、精神分裂症、癫痫、重症肌无力和先天性肌无力综合征。plics是目标Sudha Chakrapani的回应：Sudha。chakrapani@情况。edu P. Velisetty现在的地址是田纳西州孟菲斯市田纳西大学健康科学中心生理学系，田纳西州38163。帕克博士目前的地址是纽约州立大学布法罗分校生理与生物物理系，纽约州布法罗市14214。本文使用的缩略语：3-AP， 3-氨基丙醇；哦,乙酰胆碱;CW，连续波；DDM, n-dodecyl-d-maltopyranoside;双电子-电子共振；ECD，胞外结构域；ELIC，菊花欧文尼亚配体门控离子通道；EPR，电子顺磁共振；Gloeobacter violaceus配体门控离子通道；GlyR：甘氨酸受体；大分子体系的多尺度建模；MTSSL,（1-氧基- 2,2,5,5 -四甲基吡咯烷-3-基）甲基甲乙硫代磺酸盐；nAChR，烟碱乙酰胆碱受体；NiEDDA, Ni （II）乙二胺二乙酸；五聚体配体门控离子通道；RMSD，均方根偏差；TMD，跨膜结构域。
Pentameric ligand–gated ion channels (pLGICs) mediate fast synaptic transmissions in the central and peripheral nervous systems, and the vertebrate members of this family include the nicotinic acetylcholine (ACh) receptors (nAChRs), the–aminobutyric acid receptors (GABAARs), glycine receptors (GlyRs), and serotonin receptors (5HT3Rs)(Sine and Engel, 2006; Thompson et al., 2010; Corringer et al., 2012; daCosta and Baenziger, 2013). pLGICs play a key role in neuronal function associated with learning and memory, and dysfunctions in these channels underlie several neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, schizophrenia, epilepsies, myasthenia gravis, and congenital myasthenic syndromes. pLGICs are targetsCorrespondence to Sudha Chakrapani: S udha. chakrapani@ case. edu P. Velisetty’s present address is Dept. of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163. MD Parker’s present address is Dept. of Physiology and Biophysics, The State University of New York at Buffalo, Buffalo, NY 14214. Abbreviations used in this paper: 3-AP, 3-amino propanol; ACh, acetylcholine; CW, continuous wave; DDM, n-dodecyl--d-maltopyranoside; DEER, double electron–electron resonance; ECD, extracellular domain; ELIC, Erwinia chrysanthemi ligand–gated ion channel; EPR, electron paramagnetic resonance; GLIC, Gloeobacter violaceus ligand–gated ion channel; GlyR, glycine receptor; MMM, multiscale modeling of macromolecular systems; MTSSL,(1-oxyl-2, 2, 5, 5-tetramethylpyrrolidin-3-yl) methyl methanethiosulfonate; nAChR, nicotinic ACh receptor; NiEDDA, Ni (II) ethylenediamine diacetic acid; pLGIC, pentameric ligand–gated ion channel; RMSD, root mean square deviation; TMD, transmembrane domain.