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The beta subunit determines the ligand binding properties of synaptic glycine receptors.

Grudzinska, Joanna and Schemm, Rudolf and Haeger, Svenja and Nicke, Annette and Schmalzing, Guenther and Betz, Heinrich and Laube, Bodo (2005):
The beta subunit determines the ligand binding properties of synaptic glycine receptors.
In: Neuron, pp. 727-39, 45, (5), ISSN 0896-6273, [Article]

Abstract

Inhibitory glycine receptors (GlyRs) regulate motor coordination and sensory signal processing in spinal cord and other brain regions. GlyRs are pentameric proteins composed of membrane-spanning alpha and beta subunits. Here, site-directed mutagenesis combined with homology modeling based on the crystal structure of the acetylcholine binding protein identified key ligand binding residues of recombinant homooligomeric alpha1 and heterooligomeric alpha1beta GlyRs. This disclosed two highly conserved, oppositely charged residues located on adjacent subunit interfaces as being crucial for agonist binding. In addition, the beta subunit was found to determine the ligand binding properties of heterooligomeric GlyRs. Expression of an alpha1beta tandem construct and affinity purification of metabolically labeled GlyRs confirmed a subunit stoichiometry of 2alpha3beta. Because the beta subunit anchors GlyRs at synaptic sites, our results have important implications for the biosynthesis, clustering, and pharmacology of synaptic GlyRs.

Item Type: Article
Erschienen: 2005
Creators: Grudzinska, Joanna and Schemm, Rudolf and Haeger, Svenja and Nicke, Annette and Schmalzing, Guenther and Betz, Heinrich and Laube, Bodo
Title: The beta subunit determines the ligand binding properties of synaptic glycine receptors.
Language: English
Abstract:

Inhibitory glycine receptors (GlyRs) regulate motor coordination and sensory signal processing in spinal cord and other brain regions. GlyRs are pentameric proteins composed of membrane-spanning alpha and beta subunits. Here, site-directed mutagenesis combined with homology modeling based on the crystal structure of the acetylcholine binding protein identified key ligand binding residues of recombinant homooligomeric alpha1 and heterooligomeric alpha1beta GlyRs. This disclosed two highly conserved, oppositely charged residues located on adjacent subunit interfaces as being crucial for agonist binding. In addition, the beta subunit was found to determine the ligand binding properties of heterooligomeric GlyRs. Expression of an alpha1beta tandem construct and affinity purification of metabolically labeled GlyRs confirmed a subunit stoichiometry of 2alpha3beta. Because the beta subunit anchors GlyRs at synaptic sites, our results have important implications for the biosynthesis, clustering, and pharmacology of synaptic GlyRs.

Journal or Publication Title: Neuron
Volume: 45
Number: 5
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
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Date Deposited: 11 Apr 2011 09:32
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