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Coupling of a viral K+-channel with a glutamate-binding-domain highlights the modular design of ionotropic glutamate-receptors

Schönrock, Michael and Thiel, Gerhard and Laube, Bodo (2019):
Coupling of a viral K+-channel with a glutamate-binding-domain highlights the modular design of ionotropic glutamate-receptors.
In: Communications Biology, Springer Nature, 2, (1), ISSN 2399-3642, DOI: 10.1038/s42003-019-0320-y, [Online-Edition: https://doi.org/10.1038/s42003-019-0320-y],
[Article]

Abstract

Ionotropic glutamate receptors (iGluRs) mediate excitatory neuronal signaling in the mammalian CNS. These receptors are critically involved in diverse physiological processes; including learning and memory formation, as well as neuronal damage associated with neurological diseases. Based on partial sequence and structural similarities, these complex cation-permeable iGluRs are thought to descend from simple bacterial proteins emerging from a fusion of a substrate binding protein (SBP) and an inverted potassium (K+)-channel. Here, we fuse the pore module of the viral K+-channel KcvATCV-1 to the isolated glutamatebinding domain of the mammalian iGluR subunit GluA1 which is structural homolog to SBPs. The resulting chimera (GluATCV*) is functional and displays the ligand recognition characteristics of GluA1 and the K+-selectivity of KcvATCV-1. These results are consistent with a conserved activation mechanism between a glutamate-binding domain and the pore-module of a K+-channel and support the expected phylogenetic link between the two protein families.

Item Type: Article
Erschienen: 2019
Creators: Schönrock, Michael and Thiel, Gerhard and Laube, Bodo
Title: Coupling of a viral K+-channel with a glutamate-binding-domain highlights the modular design of ionotropic glutamate-receptors
Language: English
Abstract:

Ionotropic glutamate receptors (iGluRs) mediate excitatory neuronal signaling in the mammalian CNS. These receptors are critically involved in diverse physiological processes; including learning and memory formation, as well as neuronal damage associated with neurological diseases. Based on partial sequence and structural similarities, these complex cation-permeable iGluRs are thought to descend from simple bacterial proteins emerging from a fusion of a substrate binding protein (SBP) and an inverted potassium (K+)-channel. Here, we fuse the pore module of the viral K+-channel KcvATCV-1 to the isolated glutamatebinding domain of the mammalian iGluR subunit GluA1 which is structural homolog to SBPs. The resulting chimera (GluATCV*) is functional and displays the ligand recognition characteristics of GluA1 and the K+-selectivity of KcvATCV-1. These results are consistent with a conserved activation mechanism between a glutamate-binding domain and the pore-module of a K+-channel and support the expected phylogenetic link between the two protein families.

Journal or Publication Title: Communications Biology
Volume: 2
Number: 1
Publisher: Springer Nature
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
Date Deposited: 07 Apr 2019 19:55
DOI: 10.1038/s42003-019-0320-y
Official URL: https://doi.org/10.1038/s42003-019-0320-y
URN: urn:nbn:de:tuda-tuprints-86030
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