{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang H"],"funding":["Chinese Ministry of Science and Technology | Department of S and T for Social Development (Department of S&T for Social Development)","China Postdoctoral Science Foundation","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["1021-1036"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12689640"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(12)"],"pubmed_abstract":["Activation of the μ-opioid receptor (μOR) alleviates pain but also elicits adverse effects through diverse G proteins and β-arrestins. The structural details of μOR complexes with G<sub>z</sub> and β-arrestins have not been determined, impeding a comprehensive understanding of μOR signaling plasticity. Here, we present the cryo-EM structures of the μOR-G<sub>z</sub> and μOR-βarr1 complexes, revealing selective conformational preferences of μOR when engaged with specific downstream signaling transducers. Integrated receptor pharmacology, including high-resolution structural analysis, cell signaling assays, and molecular dynamics simulations, demonstrated that transmembrane helix 1 (TM1) acts as an allosteric regulator of μOR signaling bias through differential stabilization of the G<sub>i</"],"journal":["Cell research"],"pubmed_title":["The molecular basis of μ-opioid receptor signaling plasticity."],"pmcid":["PMC12689640"],"funding_grant_id":["32141004","2024M752856","82271001","2019YFA0508800","92353303","32430051"],"pubmed_authors":["Yang G","Shen Q","Ji SY","Dong Y","Zhu Y","Qin J","Zhang H","Yang M","Zang SK","Chen LN","Wu H","Zhao M","Guo J","Xi K","Zhang Y","Yu T","Wang X","Xue J","Shen DD"],"additional_accession":[]},"is_claimable":false,"name":"The molecular basis of μ-opioid receptor signaling plasticity.","description":"Activation of the μ-opioid receptor (μOR) alleviates pain but also elicits adverse effects through diverse G proteins and β-arrestins. The structural details of μOR complexes with G<sub>z</sub> and β-arrestins have not been determined, impeding a comprehensive understanding of μOR signaling plasticity. Here, we present the cryo-EM structures of the μOR-G<sub>z</sub> and μOR-βarr1 complexes, revealing selective conformational preferences of μOR when engaged with specific downstream signaling transducers. Integrated receptor pharmacology, including high-resolution structural analysis, cell signaling assays, and molecular dynamics simulations, demonstrated that transmembrane helix 1 (TM1) acts as an allosteric regulator of μOR signaling bias through differential stabilization of the G<sub>i</","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-07-15T06:36:44.457Z","creation":"2026-06-30T03:23:41.451Z"},"accession":"S-EPMC12689640","cross_references":{"pubmed":["41199005"],"doi":["10.1038/s41422-025-01191-8"]}}