{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu C"],"funding":["NIDA NIH HHS","National Institutes of Health","NIGMS NIH HHS","Canadian Institutes of Health Research","NIH HHS","CIHR"],"pagination":["878-884"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6718349"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["87(10)"],"pubmed_abstract":["The G protein-coupled μ-opioid receptor (μ-OR) mediates the majority of analgesia effects for morphine and other pain relievers. Despite extensive studies of its structure and activation mechanisms, the inherently low maturation efficiency of μ-OR represents a major hurdle to understanding its function. Here we computationally designed μ-OR mutants with altered stability to probe the relationship between cell-surface targeting, signal transduction, and agonist efficacy. The stabilizing mutation T315Y enhanced μ-OR trafficking to the plasma membrane and significantly promoted the morphine-mediated inhibition of downstream signaling. In contrast, the destabilizing mutation R165Y led to intracellular retention of μ-OR and reduced the response to morphine stimulation. These findings suggest th"],"journal":["Proteins"],"pubmed_title":["Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling."],"pmcid":["PMC6718349"],"funding_grant_id":["GM123247","R41 DA032293","R01GM114015","R01 GM114015","R01 GM123247","STTR 1R41DA032293","CERC09"],"pubmed_authors":["Linton A","Han Q","Ji RR","Samoshkin A","Faison EM","Dokholyan NV","Convertino M","Zhu C","Diatchenko L"],"additional_accession":[]},"is_claimable":false,"name":"Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling.","description":"The G protein-coupled μ-opioid receptor (μ-OR) mediates the majority of analgesia effects for morphine and other pain relievers. Despite extensive studies of its structure and activation mechanisms, the inherently low maturation efficiency of μ-OR represents a major hurdle to understanding its function. Here we computationally designed μ-OR mutants with altered stability to probe the relationship between cell-surface targeting, signal transduction, and agonist efficacy. The stabilizing mutation T315Y enhanced μ-OR trafficking to the plasma membrane and significantly promoted the morphine-mediated inhibition of downstream signaling. In contrast, the destabilizing mutation R165Y led to intracellular retention of μ-OR and reduced the response to morphine stimulation. These findings suggest th","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Oct","modification":"2026-05-03T00:13:38.211Z","creation":"2020-10-08T07:14:41Z"},"accession":"S-EPMC6718349","cross_references":{"pubmed":["31141214"],"doi":["10.1002/prot.25751"]}}