Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function

Recent studies on G-protein-coupled receptors revealed that they can dimerize. However, the role of each subunit in the activation process remains unclear. The γ-amino-n-butyric acid type B (GABA(B)) receptor is comprised of two subunits: GB1 and GB2. Both consist of an extracellular domain (ECD) an...

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Hlavní autoři: Galvez, Thierry, Duthey, Béatrice, Kniazeff, Julie, Blahos, Jaroslav, Rovelli, Giorgio, Bettler, Bernhard, Prézeau, Laurent, Pin, Jean-Philippe
Médium: Článek
Jazyk:en
Vydáno: Oxford University Press 2001
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On-line přístup:https://ncbi.nlm.nih.gov/pmc/articles/PMC125244/
https://ncbi.nlm.nih.gov/pubmed/11331581
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/emboj/20.9.2152
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spelling pubmed-1252442002-09-19 Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function Galvez, Thierry Duthey, Béatrice Kniazeff, Julie Blahos, Jaroslav Rovelli, Giorgio Bettler, Bernhard Prézeau, Laurent Pin, Jean-Philippe EMBO J Article Recent studies on G-protein-coupled receptors revealed that they can dimerize. However, the role of each subunit in the activation process remains unclear. The γ-amino-n-butyric acid type B (GABA(B)) receptor is comprised of two subunits: GB1 and GB2. Both consist of an extracellular domain (ECD) and a heptahelical domain composed of seven transmembrane α-helices, loops and the C-terminus (HD). Whereas GB1 ECD plays a critical role in ligand binding, GB2 is required not only to target GB1 subunit to the cell surface but also for receptor activation. Here, by analysing chimeric GB subunits, we show that only GB2 HD contains the determinants required for G-protein signalling. However, the HD of GB1 improves coupling efficacy. Conversely, although GB1 ECD is sufficient to bind GABA(B) ligands, the ECD of GB2 increases the agonist affinity on GB1, and is necessary for agonist activation of the receptor. These data indicate that multiple allosteric interactions between the two subunits are required for wild-type functioning of the GABA(B) receptor and highlight further the importance of the dimerization process in GPCR activation. Oxford University Press 2001-05-01 /pmc/articles/PMC125244/ /pubmed/11331581 http://dx.doi.org/10.1093/emboj/20.9.2152 Text en Copyright © 2001 European Molecular Biology Organization
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Article
spellingShingle Article
Galvez, Thierry
Duthey, Béatrice
Kniazeff, Julie
Blahos, Jaroslav
Rovelli, Giorgio
Bettler, Bernhard
Prézeau, Laurent
Pin, Jean-Philippe
Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
description Recent studies on G-protein-coupled receptors revealed that they can dimerize. However, the role of each subunit in the activation process remains unclear. The γ-amino-n-butyric acid type B (GABA(B)) receptor is comprised of two subunits: GB1 and GB2. Both consist of an extracellular domain (ECD) and a heptahelical domain composed of seven transmembrane α-helices, loops and the C-terminus (HD). Whereas GB1 ECD plays a critical role in ligand binding, GB2 is required not only to target GB1 subunit to the cell surface but also for receptor activation. Here, by analysing chimeric GB subunits, we show that only GB2 HD contains the determinants required for G-protein signalling. However, the HD of GB1 improves coupling efficacy. Conversely, although GB1 ECD is sufficient to bind GABA(B) ligands, the ECD of GB2 increases the agonist affinity on GB1, and is necessary for agonist activation of the receptor. These data indicate that multiple allosteric interactions between the two subunits are required for wild-type functioning of the GABA(B) receptor and highlight further the importance of the dimerization process in GPCR activation.
author Galvez, Thierry
Duthey, Béatrice
Kniazeff, Julie
Blahos, Jaroslav
Rovelli, Giorgio
Bettler, Bernhard
Prézeau, Laurent
Pin, Jean-Philippe
author_facet Galvez, Thierry
Duthey, Béatrice
Kniazeff, Julie
Blahos, Jaroslav
Rovelli, Giorgio
Bettler, Bernhard
Prézeau, Laurent
Pin, Jean-Philippe
author_sort Galvez, Thierry
title Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
title_short Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
title_full Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
title_fullStr Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
title_full_unstemmed Allosteric interactions between GB1 andGB2 subunits are required for optimalGABAB receptor function
title_sort allosteric interactions between gb1 andgb2 subunits are required for optimalgabab receptor function
publisher Oxford University Press
publisher_facet Oxford University Press
publishDate 2001
url https://ncbi.nlm.nih.gov/pmc/articles/PMC125244/
https://ncbi.nlm.nih.gov/pubmed/11331581
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/emboj/20.9.2152
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