大小配体的故事：五聚体配体门控离子通道与激动剂及蛋白质相互作用的最新进展
A tale of ligands big and small: an update on how pentameric ligand-gated ion channels interact with agonists and proteins.
作者信息
Pless Stephan A, Sivilotti Lucia G
机构信息
Center for Biopharmaceuticals, Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, Gower St, London WC1E 6BT, United Kingdom.
出版信息
Curr Opin Physiol. 2019 Jun 12;2:19-26. doi: 10.1016/j.cophys.2017.12.012.
Abstract
Pentameric ligand-gated ion channels (pLGICs, also known as Cys-loop receptors) are a large family of ion channels expressed in all and in several groups of bacteria and archaea. They are activated by small-molecule neurotransmitters to mediate fast transmission at many central and peripheral nervous system synapses and are the target of several drugs and insecticides. Here we review recent advances in the field, focussing on new insights on the structure of the agonist-binding site and on newly discovered protein-protein interactions involving pLGICs.
摘要
五聚体配体门控离子通道（pLGICs，也称为半胱氨酸环受体）是一类广泛存在于所有真核生物以及几组细菌和古细菌中的离子通道大家族。它们由小分子神经递质激活，在许多中枢和外周神经系统突触中介导快速传递，并且是几种药物和杀虫剂的作用靶点。在此，我们综述该领域的最新进展，重点关注激动剂结合位点结构的新见解以及涉及pLGICs的新发现的蛋白质-蛋白质相互作用。
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本文引用的文献
1
Getting a Handle on Neuropharmacology by Targeting Receptor-Associated Proteins.
Neuron. 2017 Dec 6;96(5):989-1001. doi: 10.1016/j.neuron.2017.10.001.
2
Structural basis for GABA receptor potentiation by neurosteroids.
Nat Struct Mol Biol. 2017 Nov;24(11):986-992. doi: 10.1038/nsmb.3484. Epub 2017 Oct 9.
3
Interacting amino acid replacements allow poison frogs to evolve epibatidine resistance.
Science. 2017 Sep 22;357(6357):1261-1266. doi: 10.1126/science.aan5061.
4
Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models.
Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):E8100-E8109. doi: 10.1073/pnas.1703952114. Epub 2017 Sep 5.
5
Assembly rules for GABA receptor complexes in the brain.
Elife. 2017 Aug 17;6:e27443. doi: 10.7554/eLife.27443.
6
The fifth subunit of the (α4β2) β2 nicotinic ACh receptor modulates maximal ACh responses.
Br J Pharmacol. 2018 Jun;175(11):1822-1837. doi: 10.1111/bph.13905. Epub 2017 Jul 14.
7
String method solution of the gating pathways for a pentameric ligand-gated ion channel.
Proc Natl Acad Sci U S A. 2017 May 23;114(21):E4158-E4167. doi: 10.1073/pnas.1617567114. Epub 2017 May 9.
8
Understanding structure-function relationships of the human neuronal acetylcholine receptor: insights from the first crystal structures of neuronal subunits.
Br J Pharmacol. 2018 Jun;175(11):1880-1891. doi: 10.1111/bph.13838. Epub 2017 Jun 20.
9
NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain.
Cell Rep. 2017 Apr 25;19(4):688-696. doi: 10.1016/j.celrep.2017.04.008.
10
Identification of a pre-active conformation of a pentameric channel receptor.
Elife. 2017 Mar 15;6:e23955. doi: 10.7554/eLife.23955.
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