{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:49:33Z","timestamp":1790675373142,"version":"4.1.0"},"reference-count":54,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T00:00:00Z","timestamp":1529625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DA007267"],"award-info":[{"award-number":["T32 DA007267"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["13PRE17110027"],"award-info":[{"award-number":["13PRE17110027"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007767"],"award-info":[{"award-number":["T32GM007767"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37 DA039997"],"award-info":[{"award-number":["R37 DA039997"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The intrinsic efficacy of orthosteric ligands acting at G-protein-coupled receptors (GPCRs) reflects their ability to stabilize active receptor states (R*) and is a major determinant of their physiological effects. Here, we present a direct way to quantify the efficacy of ligands by measuring the binding of a R*-specific biosensor to purified receptor employing interferometry. As an example, we use the mu-opioid receptor (\u00b5-OR), a prototypic class A GPCR, and its active state sensor, nanobody-39 (Nb39). We demonstrate that ligands vary in their ability to recruit Nb39 to \u00b5-OR and describe methadone, loperamide, and PZM21 as ligands that support unique R* conformation(s) of \u00b5-OR. We further show that positive allosteric modulators of \u00b5-OR promote formation of R* in addition to enhancing promotion by orthosteric agonists. Finally, we demonstrate that the technique can be utilized with heterotrimeric G protein. The method is cell-free, signal transduction-independent and is generally applicable to GPCRs.<\/jats:p>","DOI":"10.7554\/elife.32499","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T08:00:23Z","timestamp":1529654423000},"source":"Crossref","is-referenced-by-count":50,"title":["Measuring ligand efficacy at the mu-opioid receptor using a conformational biosensor"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8652-4045","authenticated-orcid":true,"given":"Kathryn E","family":"Livingston","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States"},{"name":"Edward F Domino Research Center, University of Michigan, Ann Arbor, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob P","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan Medical 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