%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 }