TU Darmstadt / ULB / TUbiblio

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, p. 75, 2, ISSN 2399-3642, DOI: 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 Kcv to the isolated glutamate-binding 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 Kcv. 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 Kcv to the isolated glutamate-binding 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 Kcv. 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
Divisions: 10 Department of Biology
10 Department of Biology > Plant Membrane Biophysics
10 Department of Biology > Neurophysiology and Neurosensory Systems
Date Deposited: 05 Mar 2019 06:33
DOI: 10.1038/s42003-019-0320-y
Identification Number: pmid:30820470
Export:

Optionen (nur für Redakteure)

View Item View Item