{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wingler LM"],"funding":["German Research Foundation","NEI NIH HHS","Jules Stein Professorship Endowment","Mandel Center for Hypertension and Atherosclerosis at Duke","Howard Hughes Medical Institute","German Academic Exchange Service","NHLBI NIH HHS","NINDS NIH HHS","NIH","NIGMS NIH HHS"],"pagination":["468-478.e11"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6475118"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["176(3)"],"pubmed_abstract":["\"Biased\" G protein-coupled receptor (GPCR) agonists preferentially activate pathways mediated by G proteins or β-arrestins. Here, we use double electron-electron resonance spectroscopy to probe the changes that ligands induce in the conformational distribution of the angiotensin II type I receptor. Monitoring distances between 10 pairs of nitroxide labels distributed across the intracellular regions enabled mapping of four underlying sets of conformations. Ligands from different functional classes have distinct, characteristic effects on the conformational heterogeneity of the receptor. Compared to angiotensin II, the endogenous agonist, agonists with enhanced Gq coupling more strongly stabilize an \"open\" conformation with an accessible transducer-binding site. β-arrestin-biased agonists d"],"journal":["Cell"],"pubmed_title":["Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations."],"pmcid":["PMC6475118"],"funding_grant_id":["R01GM127359","R01 NS028471","R01 GM127359","R01 EY005216","P30EY00331","R01 HL016037","R01EY005216","R01HL16037","EL779","P30 EY000331"],"pubmed_authors":["Staus DP","Lerch MT","Hilger D","Wingler LM","Lefkowitz RJ","Dror RO","Hubbell WL","Elgeti M","Latorraca NR","Kobilka BK"],"additional_accession":[]},"is_claimable":false,"name":"Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations.","description":"\"Biased\" G protein-coupled receptor (GPCR) agonists preferentially activate pathways mediated by G proteins or β-arrestins. Here, we use double electron-electron resonance spectroscopy to probe the changes that ligands induce in the conformational distribution of the angiotensin II type I receptor. Monitoring distances between 10 pairs of nitroxide labels distributed across the intracellular regions enabled mapping of four underlying sets of conformations. Ligands from different functional classes have distinct, characteristic effects on the conformational heterogeneity of the receptor. Compared to angiotensin II, the endogenous agonist, agonists with enhanced Gq coupling more strongly stabilize an \"open\" conformation with an accessible transducer-binding site. β-arrestin-biased agonists d","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2026-05-07T14:29:44.742Z","creation":"2025-04-19T16:48:34.367Z"},"accession":"S-EPMC6475118","cross_references":{"pubmed":["30639099"],"doi":["10.1016/j.cell.2018.12.005"]}}