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Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs

Bernhard, Max ; Laube, Bodo (2022)
Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs.
In: Scientific Reports, 2022, 10
doi: 10.26083/tuprints-00021126
Article, Secondary publication, Publisher's Version

Abstract

The glycine receptor (GlyR), a member of the pentameric ligand-gated ion channel family (pLGIC), displays remarkable variations in the affinity and efficacy of the full agonist glycine and the partial agonist taurine depending on the cell system used. Despite detailed insights in the GlyR three-dimensional structure and activation mechanism, little is known about conformational rearrangements induced by these agonists. Here, we characterized the conformational states of the α1 GlyR upon binding of glycine and taurine by microscale thermophoresis expressed in HEK293 cells and Xenopus oocytes after solubilization in amphipathic styrene-maleic acid copolymer nanodiscs. Our results show that glycine and taurine induce different conformational transitions of the GlyR upon ligand binding. In contrast, the variability of agonist affinity is not mediated by an altered conformational change. Thus, our data shed light on specific agonist induced conformational features and mechanisms of pLGIC upon ligand binding determining receptor activation in native environments.

Item Type: Article
Erschienen: 2022
Creators: Bernhard, Max ; Laube, Bodo
Type of entry: Secondary publication
Title: Thermophoretic analysis of ligand-specific conformational states of the inhibitory glycine receptor embedded in copolymer nanodiscs
Language: English
Date: 2022
Year of primary publication: 2022
Publisher: Springer Nature
Journal or Publication Title: Scientific Reports
Volume of the journal: 10
Collation: 11 Seiten
DOI: 10.26083/tuprints-00021126
URL / URN: https://tuprints.ulb.tu-darmstadt.de/21126
Corresponding Links:
Origin: Secondary publication via sponsored Golden Open Access
Abstract:

The glycine receptor (GlyR), a member of the pentameric ligand-gated ion channel family (pLGIC), displays remarkable variations in the affinity and efficacy of the full agonist glycine and the partial agonist taurine depending on the cell system used. Despite detailed insights in the GlyR three-dimensional structure and activation mechanism, little is known about conformational rearrangements induced by these agonists. Here, we characterized the conformational states of the α1 GlyR upon binding of glycine and taurine by microscale thermophoresis expressed in HEK293 cells and Xenopus oocytes after solubilization in amphipathic styrene-maleic acid copolymer nanodiscs. Our results show that glycine and taurine induce different conformational transitions of the GlyR upon ligand binding. In contrast, the variability of agonist affinity is not mediated by an altered conformational change. Thus, our data shed light on specific agonist induced conformational features and mechanisms of pLGIC upon ligand binding determining receptor activation in native environments.

Status: Publisher's Version
URN: urn:nbn:de:tuda-tuprints-211262
Classification DDC: 500 Science and mathematics > 500 Science
600 Technology, medicine, applied sciences > 600 Technology
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
Interdisziplinäre Forschungsprojekte
Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology
Date Deposited: 14 Apr 2022 12:12
Last Modified: 19 Apr 2022 05:18
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