Understanding the Ligand-Receptor-G Protein Ternary Complex for GPCR Drug Discovery. Export

@article{citeulike:4958621, abstract = {Understanding the ternary complex between G protein-coupled receptors (GPCRs), cognate G proteins, and their ligands is an important landmark for drug discovery. Yet, little is known about the specific interactions between GPCRs and G proteins. For a better perspective on the ternary complex dynamics, we adapted a beta(2)-adrenergic receptor(beta(2)AR)-tetGs(alpha) reconstitution system and found evidence that for efficient coupling of the beta(2)AR to Gs does not require specific interactions between the betagamma-subunits and the beta(2)AR. Our results demonstrate that specific interactions between betagamma and the beta(2)AR are not required for G protein activation but likely serve to anchor Gs(alpha) to the plasma membrane. Our results also suggests that the advantages of analysis of G protein activation by using beta(2)AR receptor-tetGs(alpha) system in vitro at the close proximity of the receptor may constitute a simple screening system that avoids false positives and potentially adapted to screen drugs for other GPCRs.}, author = {Ratnala, V. R. and Kobilka, B.}, citeulike-article-id = {4958621}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/978-1-60327-317-6_5}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19513642}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19513642}, doi = {10.1007/978-1-60327-317-6_5}, issn = {1064-3745}, journal = {Methods in molecular biology (Clifton, N.J.)}, keywords = {activation, gpcr, review}, pages = {67--77}, posted-at = {2009-06-25 16:46:39}, priority = {2}, title = {Understanding the Ligand-Receptor-G Protein Ternary Complex for GPCR Drug Discovery.}, url = {http://dx.doi.org/10.1007/978-1-60327-317-6_5}, volume = {552}, year = {2009} }

TY - JOUR ID - citeulike:4958621 L3 - citeulike-article-id:4958621 N2 - Understanding the ternary complex between G protein-coupled receptors (GPCRs), cognate G proteins, and their ligands is an important landmark for drug discovery. Yet, little is known about the specific interactions between GPCRs and G proteins. For a better perspective on the ternary complex dynamics, we adapted a beta(2)-adrenergic receptor(beta(2)AR)-tetGs(alpha) reconstitution system and found evidence that for efficient coupling of the beta(2)AR to Gs does not require specific interactions between the betagamma-subunits and the beta(2)AR. Our results demonstrate that specific interactions between betagamma and the beta(2)AR are not required for G protein activation but likely serve to anchor Gs(alpha) to the plasma membrane. Our results also suggests that the advantages of analysis of G protein activation by using beta(2)AR receptor-tetGs(alpha) system in vitro at the close proximity of the receptor may constitute a simple screening system that avoids false positives and potentially adapted to screen drugs for other GPCRs. JF - Methods in molecular biology (Clifton, N.J.) SN - 1064-3745 EP - 77 TI - Understanding the Ligand-Receptor-G Protein Ternary Complex for GPCR Drug Discovery. VL - 552 SP - 67 KW - activation KW - gpcr KW - review AU - Ratnala, VR AU - Kobilka, B PY - 2009/// UR - http://dx.doi.org/10.1007/978-1-60327-317-6_5 ER -