Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. Export

@article{citeulike:5817700, abstract = {The beta(2)-adrenoceptor (beta(2)AR) was one of the first Family A G protein-coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we still know little about the number and arrangement of protomers in oligomers, the influence of ligands on the organization or stability of oligomers, or the requirement for other proteins to promote oligomerization. We used fluorescence resonance energy transfer (FRET) to characterize the oligomerization of purified beta(2)AR site-specifically labelled at three different positions with fluorophores and reconstituted into a model lipid bilayer. Our results suggest that the beta(2)AR is predominantly tetrameric following reconstitution into phospholipid vesicles. Agonists and antagonists have little effect on the relative orientation of protomers in oligomeric complexes. In contrast, binding of inverse agonists leads to significant increases in FRET efficiencies for most labelling pairs, suggesting that this class of ligand promotes tighter packing of protomers and/or the formation of more complex oligomers by reducing conformational fluctuations in individual protomers. The results provide new structural insights into beta(2)AR oligomerization and suggest a possible mechanism for the functional effects of inverse agonists.}, author = {Fung, Juan Jos\'{e} J. and Deupi, Xavier and Pardo, Leonardo and Yao, Xiao Jie J. and Velez-Ruiz, Gisselle A. and Devree, Brian T. and Sunahara, Roger K. and Kobilka, Brian K.}, citeulike-article-id = {5817700}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2009.267}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19763081}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19763081}, day = {17}, doi = {10.1038/emboj.2009.267}, issn = {1460-2075}, journal = {The EMBO journal}, keywords = {agonist, antagonist, b2ar, fret, inverse\_agonist, oligomerization}, month = {September}, posted-at = {2009-10-06 19:26:56}, priority = {2}, publisher = {Nature Publishing Group}, title = {Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer.}, url = {http://dx.doi.org/10.1038/emboj.2009.267}, year = {2009} }

TY - JOUR ID - citeulike:5817700 L3 - citeulike-article-id:5817700 N2 - The beta(2)-adrenoceptor (beta(2)AR) was one of the first Family A G protein-coupled receptors (GPCRs) shown to form oligomers in cellular membranes, yet we still know little about the number and arrangement of protomers in oligomers, the influence of ligands on the organization or stability of oligomers, or the requirement for other proteins to promote oligomerization. We used fluorescence resonance energy transfer (FRET) to characterize the oligomerization of purified beta(2)AR site-specifically labelled at three different positions with fluorophores and reconstituted into a model lipid bilayer. Our results suggest that the beta(2)AR is predominantly tetrameric following reconstitution into phospholipid vesicles. Agonists and antagonists have little effect on the relative orientation of protomers in oligomeric complexes. In contrast, binding of inverse agonists leads to significant increases in FRET efficiencies for most labelling pairs, suggesting that this class of ligand promotes tighter packing of protomers and/or the formation of more complex oligomers by reducing conformational fluctuations in individual protomers. The results provide new structural insights into beta(2)AR oligomerization and suggest a possible mechanism for the functional effects of inverse agonists. JF - The EMBO journal SN - 1460-2075 TI - Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. PB - Nature Publishing Group KW - agonist KW - antagonist KW - b2ar KW - fret KW - inverse_agonist KW - oligomerization AU - Fung, Juan José AU - Deupi, Xavier AU - Pardo, Leonardo AU - Yao, Xiao Jie AU - Velez-Ruiz, Gisselle AU - Devree, Brian AU - Sunahara, Roger AU - Kobilka, Brian PY - 2009/09/17/ UR - http://dx.doi.org/10.1038/emboj.2009.267 ER -