Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic
receptor and Gi-protein heterotrimer
V. Nikolaev, C. Hoffmann, M. Bunemann, M. Lohse, and J. Vilardaga. J Biol Chem, 281 (34):
24506-11(August 2006)Nikolaev, Viacheslav O Hoffmann, Carsten Bunemann, Moritz Lohse,
Martin J Vilardaga, Jean-Pierre Research Support, Non-U.S. Gov't
United States The Journal of biological chemistry J Biol Chem. 2006
Aug 25;281(34):24506-11. Epub 2006 Jun 20..
Abstract
To characterize the mechanism by which heterotrimeric G-proteins interpret
the signals coming from various neurotransmitters of diverse efficacies
(agonists and partial agonists) acting on alpha(2A)-adrenergic receptors,
we used a fluorescent resonance energy transfer-based approach to
study the effects of these partial agonists on the activation process
of both the alpha(2A)-adrenergic receptor and its cognate G(i)-protein.
We show that ligands of different efficacies switch the receptor
into distinct conformational states, which in turn set the speed
and extent of the G(i)-protein signaling. Thus, in cells the efficacy
by which a receptor responds to diverse ligands is caused by the
ability of the G-protein to differentiate between distinct receptor
conformations. The data provide a new key characteristic underlying
the mechanism of partial agonism at G-protein-coupled receptors.
Nikolaev, Viacheslav O Hoffmann, Carsten Bunemann, Moritz Lohse,
Martin J Vilardaga, Jean-Pierre Research Support, Non-U.S. Gov't
United States The Journal of biological chemistry J Biol Chem. 2006
Aug 25;281(34):24506-11. Epub 2006 Jun 20.
%0 Journal Article
%1 Nikolaev2006b
%A Nikolaev, V. O.
%A Hoffmann, C.
%A Bunemann, M.
%A Lohse, M. J.
%A Vilardaga, J. P.
%D 2006
%J J Biol Chem
%K Animals Conformation Fusion GTP-Binding Gi-Go/*agonists/*chemistry/genetics Humans Kinetics Ligands Mice Protein Proteins Recombinant Relationship Signal Structure-Activity Subunits, Transduction alpha alpha-2/*agonists/*chemistry/genetics Receptor Adrenergic
%N 34
%P 24506-11
%T Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic
receptor and Gi-protein heterotrimer
%U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16787921
%V 281
%X To characterize the mechanism by which heterotrimeric G-proteins interpret
the signals coming from various neurotransmitters of diverse efficacies
(agonists and partial agonists) acting on alpha(2A)-adrenergic receptors,
we used a fluorescent resonance energy transfer-based approach to
study the effects of these partial agonists on the activation process
of both the alpha(2A)-adrenergic receptor and its cognate G(i)-protein.
We show that ligands of different efficacies switch the receptor
into distinct conformational states, which in turn set the speed
and extent of the G(i)-protein signaling. Thus, in cells the efficacy
by which a receptor responds to diverse ligands is caused by the
ability of the G-protein to differentiate between distinct receptor
conformations. The data provide a new key characteristic underlying
the mechanism of partial agonism at G-protein-coupled receptors.
@article{Nikolaev2006b,
abstract = {To characterize the mechanism by which heterotrimeric G-proteins interpret
the signals coming from various neurotransmitters of diverse efficacies
(agonists and partial agonists) acting on alpha(2A)-adrenergic receptors,
we used a fluorescent resonance energy transfer-based approach to
study the effects of these partial agonists on the activation process
of both the alpha(2A)-adrenergic receptor and its cognate G(i)-protein.
We show that ligands of different efficacies switch the receptor
into distinct conformational states, which in turn set the speed
and extent of the G(i)-protein signaling. Thus, in cells the efficacy
by which a receptor responds to diverse ligands is caused by the
ability of the G-protein to differentiate between distinct receptor
conformations. The data provide a new key characteristic underlying
the mechanism of partial agonism at G-protein-coupled receptors.},
added-at = {2010-12-14T18:12:02.000+0100},
author = {Nikolaev, V. O. and Hoffmann, C. and Bunemann, M. and Lohse, M. J. and Vilardaga, J. P.},
biburl = {https://www.bibsonomy.org/bibtex/2f69dac2bab58d3f6d1d25e43449ed70b/pharmawuerz},
endnotereftype = {Journal Article},
interhash = {85e9599daf0f37ce75638617437a4c25},
intrahash = {f69dac2bab58d3f6d1d25e43449ed70b},
issn = {0021-9258 (Print) 0021-9258 (Linking)},
journal = {J Biol Chem},
keywords = {Animals Conformation Fusion GTP-Binding Gi-Go/*agonists/*chemistry/genetics Humans Kinetics Ligands Mice Protein Proteins Recombinant Relationship Signal Structure-Activity Subunits, Transduction alpha alpha-2/*agonists/*chemistry/genetics Receptor Adrenergic},
month = {Aug 25},
note = {Nikolaev, Viacheslav O Hoffmann, Carsten Bunemann, Moritz Lohse,
Martin J Vilardaga, Jean-Pierre Research Support, Non-U.S. Gov't
United States The Journal of biological chemistry J Biol Chem. 2006
Aug 25;281(34):24506-11. Epub 2006 Jun 20.},
number = 34,
pages = {24506-11},
shorttitle = {Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic
receptor and Gi-protein heterotrimer},
timestamp = {2010-12-14T18:22:41.000+0100},
title = {Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic
receptor and Gi-protein heterotrimer},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16787921},
volume = 281,
year = 2006
}