{"id":"https://openalex.org/W7124178079","doi":"https://doi.org/10.1038/s41586-025-09963-3","title":"Ligand-specific activation trajectories dictate GPCR signalling in cells","display_name":"Ligand-specific activation trajectories dictate GPCR signalling in cells","publication_year":2026,"publication_date":"2026-01-14","ids":{"openalex":"https://openalex.org/W7124178079","doi":"https://doi.org/10.1038/s41586-025-09963-3","pmid":"https://pubmed.ncbi.nlm.nih.gov/41535472"},"language":"en","primary_location":{"id":"doi:10.1038/s41586-025-09963-3","doi":"https://doi.org/10.1038/s41586-025-09963-3","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41586-025-09963-3","pdf_url":null,"source":{"id":"https://openalex.org/S137773608","display_name":"Nature","issn_l":"0028-0836","issn":["0028-0836","1476-4687"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nature","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","datacite","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1038/s41586-025-09963-3","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5082738748","display_name":"Romy Thomas","orcid":"https://orcid.org/0000-0001-8663-3682","observed_orcids":["https://orcid.org/0000-0001-8663-3682"]},"institutions":[{"id":"https://openalex.org/I205582932","display_name":"Max Delbr\u00fcck Center","ror":"https://ror.org/04p5ggc03","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I205582932"]},{"id":"https://openalex.org/I4210137306","display_name":"Stanford Medicine","ror":"https://ror.org/03mtd9a03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]},{"id":"https://openalex.org/I97018004","display_name":"Stanford University","ror":"https://ror.org/00f54p054","country_code":"US","type":"education","lineage":["https://openalex.org/I97018004"]}],"countries":["DE","US"],"is_corresponding":false,"raw_author_name":"Romy Thomas","raw_affiliation_strings":["Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA","Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany","Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany"],"raw_orcid":"https://orcid.org/0000-0001-8663-3682","affiliations":[{"raw_affiliation_string":"Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA","institution_ids":["https://openalex.org/I4210137306","https://openalex.org/I97018004"]},{"raw_affiliation_string":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany","institution_ids":["https://openalex.org/I205582932"]},{"raw_affiliation_string":"Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5123024211","display_name":"Pauline S. Jacoby","orcid":"https://orcid.org/0009-0008-2466-465X","observed_orcids":["https://orcid.org/0009-0008-2466-465X"]},"institutions":[{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Pauline S. Jacoby","raw_affiliation_strings":["Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany"],"raw_orcid":"https://orcid.org/0009-0008-2466-465X","affiliations":[{"raw_affiliation_string":"Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081969725","display_name":"Chiara De Faveri","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I137479271","display_name":"Helmholtz Centre for Environmental Research","ror":"https://ror.org/000h6jb29","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I137479271"]},{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Chiara De Faveri","raw_affiliation_strings":["Department of Molecular Environmental Biotechnology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany","Institute of Biochemistry, Leipzig University, Leipzig, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Molecular Environmental Biotechnology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany","institution_ids":["https://openalex.org/I137479271"]},{"raw_affiliation_string":"Institute of Biochemistry, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068475182","display_name":"C\u00e9cile Derieux","orcid":"https://orcid.org/0000-0002-2743-4023","observed_orcids":["https://orcid.org/0000-0002-2743-4023"]},"institutions":[{"id":"https://openalex.org/I197323543","display_name":"Johannes Gutenberg University Mainz","ror":"https://ror.org/023b0x485","country_code":"DE","type":"education","lineage":["https://openalex.org/I197323543"]},{"id":"https://openalex.org/I4210094062","display_name":"University Medical Center of the Johannes Gutenberg University Mainz","ror":"https://ror.org/00q1fsf04","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I4210094062"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"C\u00e9cile Derieux","raw_affiliation_strings":["Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"],"raw_orcid":"https://orcid.org/0000-0002-2743-4023","affiliations":[{"raw_affiliation_string":"Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany","institution_ids":["https://openalex.org/I197323543","https://openalex.org/I4210094062"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5056781371","display_name":"Aenne\u2010Dorothea Liebing","orcid":"https://orcid.org/0009-0003-2882-4386","observed_orcids":["https://orcid.org/0009-0003-2882-4386"]},"institutions":[{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Aenne-Dorothea Liebing","raw_affiliation_strings":["Rudolf-Sch\u00f6nheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany"],"raw_orcid":"https://orcid.org/0009-0003-2882-4386","affiliations":[{"raw_affiliation_string":"Rudolf-Sch\u00f6nheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002349821","display_name":"Barbora Melkes","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I197323543","display_name":"Johannes Gutenberg University Mainz","ror":"https://ror.org/023b0x485","country_code":"DE","type":"education","lineage":["https://openalex.org/I197323543"]},{"id":"https://openalex.org/I4210094062","display_name":"University Medical Center of the Johannes Gutenberg University Mainz","ror":"https://ror.org/00q1fsf04","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I4210094062"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Barbora Melkes","raw_affiliation_strings":["Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany","institution_ids":["https://openalex.org/I197323543","https://openalex.org/I4210094062"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5123039642","display_name":"Hans-Joachim Martini","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I197323543","display_name":"Johannes Gutenberg University Mainz","ror":"https://ror.org/023b0x485","country_code":"DE","type":"education","lineage":["https://openalex.org/I197323543"]},{"id":"https://openalex.org/I4210094062","display_name":"University Medical Center of the Johannes Gutenberg University Mainz","ror":"https://ror.org/00q1fsf04","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I4210094062"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Hans-Joachim Martini","raw_affiliation_strings":["Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany","institution_ids":["https://openalex.org/I197323543","https://openalex.org/I4210094062"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5013807967","display_name":"Marcel Berm\u00fadez","orcid":"https://orcid.org/0000-0002-7421-3282","observed_orcids":["https://orcid.org/0000-0002-7421-3282"]},"institutions":[{"id":"https://openalex.org/I22465464","display_name":"University of M\u00fcnster","ror":"https://ror.org/00pd74e08","country_code":"DE","type":"education","lineage":["https://openalex.org/I22465464"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Marcel Berm\u00fadez","raw_affiliation_strings":["Institute for Pharmaceutical and Medical Chemistry, Faculty of Chemistry and Pharmacy, University of M\u00fcnster, M\u00fcnster, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Institute for Pharmaceutical and Medical Chemistry, Faculty of Chemistry and Pharmacy, University of M\u00fcnster, M\u00fcnster, Germany","institution_ids":["https://openalex.org/I22465464"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065543516","display_name":"Claudia St\u00e4ubert","orcid":"https://orcid.org/0000-0003-0721-8507","observed_orcids":["https://orcid.org/0000-0003-0721-8507"]},"institutions":[{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Claudia St\u00e4ubert","raw_affiliation_strings":["Rudolf-Sch\u00f6nheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany"],"raw_orcid":"https://orcid.org/0000-0003-0721-8507","affiliations":[{"raw_affiliation_string":"Rudolf-Sch\u00f6nheimer Institute of Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085011132","display_name":"Martin J. Lohse","orcid":"https://orcid.org/0000-0002-0599-3510","observed_orcids":["https://orcid.org/0000-0002-0599-3510"]},"institutions":[{"id":"https://openalex.org/I205582932","display_name":"Max Delbr\u00fcck Center","ror":"https://ror.org/04p5ggc03","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I205582932"]},{"id":"https://openalex.org/I62916508","display_name":"Technical University of Munich","ror":"https://ror.org/02kkvpp62","country_code":"DE","type":"education","lineage":["https://openalex.org/I62916508"]},{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Martin J. Lohse","raw_affiliation_strings":["ISAR Bioscience Institute, Planegg, Germany","Institute of Regenerative Medicine in Cardiology-Technical University of Munich, Munich, Germany","Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany","Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"ISAR Bioscience Institute, Planegg, Germany","institution_ids":[]},{"raw_affiliation_string":"Institute of Regenerative Medicine in Cardiology-Technical University of Munich, Munich, Germany","institution_ids":["https://openalex.org/I62916508"]},{"raw_affiliation_string":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany","institution_ids":["https://openalex.org/I205582932"]},{"raw_affiliation_string":"Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031204429","display_name":"Irene Coin","orcid":"https://orcid.org/0000-0002-7722-004X","observed_orcids":["https://orcid.org/0000-0002-7722-004X"]},"institutions":[{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Irene Coin","raw_affiliation_strings":["Institute of Biochemistry, Leipzig University, Leipzig, Germany. irene.coin@uni-leipzig.de"],"raw_orcid":"https://orcid.org/0000-0002-7722-004X","affiliations":[{"raw_affiliation_string":"Institute of Biochemistry, Leipzig University, Leipzig, Germany. irene.coin@uni-leipzig.de","institution_ids":["https://openalex.org/I926574661"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5126393315","display_name":"Andreas Bock","orcid":"https://orcid.org/0000-0002-6344-6494","observed_orcids":["https://orcid.org/0000-0002-6344-6494"]},"institutions":[{"id":"https://openalex.org/I197323543","display_name":"Johannes Gutenberg University Mainz","ror":"https://ror.org/023b0x485","country_code":"DE","type":"education","lineage":["https://openalex.org/I197323543"]},{"id":"https://openalex.org/I205582932","display_name":"Max Delbr\u00fcck Center","ror":"https://ror.org/04p5ggc03","country_code":"DE","type":"facility","lineage":["https://openalex.org/I1305996414","https://openalex.org/I205582932"]},{"id":"https://openalex.org/I4210094062","display_name":"University Medical Center of the Johannes Gutenberg University Mainz","ror":"https://ror.org/00q1fsf04","country_code":"DE","type":"healthcare","lineage":["https://openalex.org/I4210094062"]},{"id":"https://openalex.org/I926574661","display_name":"Leipzig University","ror":"https://ror.org/03s7gtk40","country_code":"DE","type":"education","lineage":["https://openalex.org/I926574661"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Andreas Bock","raw_affiliation_strings":["Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. andreas.bock@uni-mainz.de","Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. andreas.bock@uni-mainz.de","Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. andreas.bock@uni-mainz.de","Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany. andreas.bock@uni-mainz.de"],"raw_orcid":"https://orcid.org/0000-0002-6344-6494","affiliations":[{"raw_affiliation_string":"Institute of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. andreas.bock@uni-mainz.de","institution_ids":["https://openalex.org/I197323543","https://openalex.org/I4210094062"]},{"raw_affiliation_string":"Max-Delbr\u00fcck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. andreas.bock@uni-mainz.de","institution_ids":["https://openalex.org/I205582932"]},{"raw_affiliation_string":"Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. andreas.bock@uni-mainz.de","institution_ids":["https://openalex.org/I197323543","https://openalex.org/I4210094062"]},{"raw_affiliation_string":"Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, Leipzig University, Leipzig, Germany. andreas.bock@uni-mainz.de","institution_ids":["https://openalex.org/I926574661"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":9,"corresponding_author_ids":["https://openalex.org/A5031204429","https://openalex.org/A5126393315"],"corresponding_institution_ids":["https://openalex.org/I197323543","https://openalex.org/I205582932","https://openalex.org/I4210094062","https://openalex.org/I926574661"],"apc_list":{"value":12690,"currency":"USD","value_usd":12690},"apc_paid":{"value":12690,"currency":"USD","value_usd":12690},"fwci":22.2891,"has_fulltext":false,"cited_by_count":12,"citation_normalized_percentile":{"value":0.99649339,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":99,"max":100},"biblio":{"volume":"650","issue":"8103","first_page":"1053","last_page":"1062"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10077","display_name":"Neuroscience and Neuropharmacology Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/g-protein-coupled-receptors","display_name":"G protein-coupled receptors","score":0.9980000257492065},{"id":"https://openalex.org/keywords/m2-muscarinic-receptor","display_name":"M2 muscarinic receptor","score":0.9369999766349792},{"id":"https://openalex.org/keywords/ligand-efficacy","display_name":"ligand efficacy","score":0.8709999918937683},{"id":"https://openalex.org/keywords/g-protein-activation","display_name":"G protein activation","score":0.6439999938011169},{"id":"https://openalex.org/keywords/g-protein-selectivity","display_name":"G protein selectivity","score":0.7390000224113464},{"id":"https://openalex.org/keywords/receptor-g-protein-complex","display_name":"receptor-G protein complex","score":0.5929999947547913},{"id":"https://openalex.org/keywords/biosensors","display_name":"biosensors","score":0.5559999942779541},{"id":"https://openalex.org/keywords/genetic-code-expansion","display_name":"genetic code expansion","score":0.7739999890327454}],"concepts":[{"id":"https://openalex.org/C135285700","wikidata":"https://www.wikidata.org/wiki/Q38173","display_name":"G protein-coupled receptor","level":3,"score":0.8348000049591064},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.6107000112533569},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.5327000021934509},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.48179998993873596},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.46720001101493835},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4514000117778778},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.4262999892234802},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.4185999929904938},{"id":"https://openalex.org/C39743133","wikidata":"https://www.wikidata.org/wiki/Q3262595","display_name":"Signalling","level":2,"score":0.41440001130104065},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.3767000138759613},{"id":"https://openalex.org/C33789571","wikidata":"https://www.wikidata.org/wiki/Q410959","display_name":"Muscarinic acetylcholine receptor","level":3,"score":0.3750999867916107},{"id":"https://openalex.org/C166342909","wikidata":"https://www.wikidata.org/wiki/Q845326","display_name":"Allosteric regulation","level":3,"score":0.3582000136375427},{"id":"https://openalex.org/C160756335","wikidata":"https://www.wikidata.org/wiki/Q669391","display_name":"Biosensor","level":2,"score":0.3546999990940094},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.34369999170303345},{"id":"https://openalex.org/C79879829","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Intracellular","level":2,"score":0.34279999136924744},{"id":"https://openalex.org/C64615621","wikidata":"https://www.wikidata.org/wiki/Q15333405","display_name":"Muscarinic acetylcholine receptor M5","level":5,"score":0.32989999651908875},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.319599986076355},{"id":"https://openalex.org/C80161118","wikidata":"https://www.wikidata.org/wiki/Q408520","display_name":"Acetylcholine receptor","level":3,"score":0.31349998712539673},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.3109999895095825},{"id":"https://openalex.org/C930959","wikidata":"https://www.wikidata.org/wiki/Q4086920","display_name":"Bioorthogonal chemistry","level":3,"score":0.3050999939441681},{"id":"https://openalex.org/C150555746","wikidata":"https://www.wikidata.org/wiki/Q210973","display_name":"Cell signaling","level":3,"score":0.29980000853538513},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.29660001397132874},{"id":"https://openalex.org/C2775910092","wikidata":"https://www.wikidata.org/wiki/Q180623","display_name":"Acetylcholine","level":2,"score":0.28859999775886536},{"id":"https://openalex.org/C197462201","wikidata":"https://www.wikidata.org/wiki/Q2476074","display_name":"Cell surface receptor","level":3,"score":0.27799999713897705},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.27649998664855957},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.27140000462532043},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.2671999931335449},{"id":"https://openalex.org/C3018449070","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signalling pathways","level":3,"score":0.26339998841285706}],"mesh":[],"locations_count":6,"locations":[{"id":"doi:10.1038/s41586-025-09963-3","doi":"https://doi.org/10.1038/s41586-025-09963-3","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41586-025-09963-3","pdf_url":null,"source":{"id":"https://openalex.org/S137773608","display_name":"Nature","issn_l":"0028-0836","issn":["0028-0836","1476-4687"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nature","raw_type":"journal-article"},{"id":"pmid:41535472","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41535472","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nature","raw_type":"Journal Article"},{"id":"pmh:oai:edoc.mdc-berlin.de:26103","doi":null,"is_oa":false,"landing_page_url":"https://orcid.org/0000-0001-8663-3682","pdf_url":null,"source":{"id":"https://openalex.org/S4306400224","display_name":"MDC Repository (Max-Delbrueck-Center for Molecular Medicine)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I149899117","host_organization_name":"Max Planck Society","host_organization_lineage":["https://openalex.org/I149899117"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Article"},{"id":"pmh:oai:openscience.ub.uni-mainz.de:20.500.12030/15964","doi":null,"is_oa":true,"landing_page_url":"https://openscience.ub.uni-mainz.de/handle/20.500.12030/15964","pdf_url":null,"source":{"id":"https://openalex.org/S7407055239","display_name":"Gutenberg Open Science","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Nature. 650. -. 2026. 1053. 1062. -","raw_type":"publishedVersion"},{"id":"pmh:oai:pubmedcentral.nih.gov:12935549","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12935549/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Nature","raw_type":"Text"},{"id":"doi:10.25358/openscience-15943","doi":"https://doi.org/10.25358/openscience-15943","is_oa":true,"landing_page_url":"https://doi.org/10.25358/openscience-15943","pdf_url":null,"source":{"id":"https://openalex.org/S7407055239","display_name":"Gutenberg Open Science","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":null,"raw_source_name":null,"raw_type":"JournalArticle"}],"best_oa_location":{"id":"doi:10.1038/s41586-025-09963-3","doi":"https://doi.org/10.1038/s41586-025-09963-3","is_oa":true,"landing_page_url":"https://doi.org/10.1038/s41586-025-09963-3","pdf_url":null,"source":{"id":"https://openalex.org/S137773608","display_name":"Nature","issn_l":"0028-0836","issn":["0028-0836","1476-4687"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319908","host_organization_name":"Nature Portfolio","host_organization_lineage":["https://openalex.org/P4310319908","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Nature Portfolio","Springer Nature"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Nature","raw_type":"journal-article"},"sustainable_development_goals":[],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":67,"referenced_works":["https://openalex.org/W1136490972","https://openalex.org/W1507101852","https://openalex.org/W1511344849","https://openalex.org/W1603274157","https://openalex.org/W1605393199","https://openalex.org/W1962808243","https://openalex.org/W1964626085","https://openalex.org/W1969027187","https://openalex.org/W1970613671","https://openalex.org/W1971439989","https://openalex.org/W1973029121","https://openalex.org/W1979632514","https://openalex.org/W1988097700","https://openalex.org/W1993684492","https://openalex.org/W2000781683","https://openalex.org/W2011301426","https://openalex.org/W2016122189","https://openalex.org/W2047567287","https://openalex.org/W2051994079","https://openalex.org/W2075947666","https://openalex.org/W2078897114","https://openalex.org/W2099540110","https://openalex.org/W2102459914","https://openalex.org/W2103346924","https://openalex.org/W2111889757","https://openalex.org/W2116803443","https://openalex.org/W2134796998","https://openalex.org/W2140985762","https://openalex.org/W2150715718","https://openalex.org/W2153167479","https://openalex.org/W2162109316","https://openalex.org/W2168335282","https://openalex.org/W2332024781","https://openalex.org/W2345966590","https://openalex.org/W2471992026","https://openalex.org/W2474393700","https://openalex.org/W2528392802","https://openalex.org/W2616139473","https://openalex.org/W2624652951","https://openalex.org/W2765153686","https://openalex.org/W2770490738","https://openalex.org/W2777807685","https://openalex.org/W2809303314","https://openalex.org/W2897059447","https://openalex.org/W2910817182","https://openalex.org/W2944371911","https://openalex.org/W2944643389","https://openalex.org/W2944677299","https://openalex.org/W2944707277","https://openalex.org/W2946407865","https://openalex.org/W2998756805","https://openalex.org/W3001385578","https://openalex.org/W3014501695","https://openalex.org/W3022812876","https://openalex.org/W3035965352","https://openalex.org/W3083406432","https://openalex.org/W3121729579","https://openalex.org/W3137473376","https://openalex.org/W4221100832","https://openalex.org/W4317804518","https://openalex.org/W4320855458","https://openalex.org/W4323834788","https://openalex.org/W4394688722","https://openalex.org/W4399586164","https://openalex.org/W4401184212","https://openalex.org/W4402269939","https://openalex.org/W4404131474"],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"G-protein-coupled":[1],"receptors":[2],"(GPCRs)":[3],"are":[4],"key":[5],"mediators":[6],"of":[7,16,36,84,105,124,131,148,180],"cell":[8],"communication":[9],"and":[10,39,58,76,164,168,193],"represent":[11],"the":[12,91,110,132,177],"most":[13],"important":[14],"class":[15],"drug":[17,202],"targets":[18],"1,2":[19],".":[20,52],"Biophysical":[21],"studies":[22],"with":[23,138],"purified":[24],"GPCRs":[25],"in":[26,33,47,64,114,183],"vitro":[27],"have":[28],"suggested":[29],"that":[30,119,160],"they":[31],"exist":[32],"an":[34,48],"equilibrium":[35],"distinct":[37,128],"inactive":[38],"active":[40,129],"states,":[41],"which":[42],"is":[43,56],"modulated":[44],"by":[45],"ligands":[46],"efficacy-dependent":[49],"manner":[50],"3\u201311":[51],"However,":[53],"how":[54],"efficacy":[55,182],"encoded":[57],"whether":[59],"multiple":[60],"receptor":[61,96],"states":[62,130],"occur":[63],"living":[65],"cells":[66],"remain":[67],"unclear.":[68],"Here":[69],"we":[70],"use":[71],"genetic":[72],"code":[73],"expansion":[74],"12":[75],"bioorthogonal":[77],"labelling":[78],"13\u201316":[79],"to":[80,142,170],"generate":[81],"a":[82,88,139],"panel":[83],"fluorescence-based":[85],"biosensors":[86,101],"for":[87,200],"prototypical":[89],"GPCR,":[90],"M":[92,134,150],"2":[93,98,135,151],"muscarinic":[94],"acetylcholine":[95],"(M":[97],"R).":[99],"These":[100,174],"enable":[102],"real-time":[103],"monitoring":[104],"agonist-promoted":[106],"conformational":[107,166,194],"changes":[108,167],"across":[109],"receptor\u2019s":[111],"extracellular":[112],"surface":[113],"intact":[115,184],"cells.":[116,185],"We":[117],"demonstrate":[118],"different":[120,140,189],"agonists":[121],"produce":[122],"equilibria":[123,195],"at":[125],"least":[126],"four":[127],"G-protein-bound":[133],"R,":[136],"each":[137],"ability":[141],"activate":[143],"G":[144],"proteins.":[145],"The":[146],"formation":[147],"these":[149],"R\u2013G-protein":[152],"complexes":[153],"occurs":[154],"over":[155],"0.2\u20135":[156],"s":[157],"along":[158],"trajectories":[159,192],"involve":[161],"both":[162],"common":[163],"ligand-specific":[165],"appear":[169],"determine":[171],"G-protein":[172],"selectivity.":[173],"observations":[175],"reveal":[176],"molecular":[178],"nature":[179],"ligand":[181],"Selectively":[186],"exploiting":[187],"such":[188],"GPCR":[190,201],"activation":[191],"may":[196],"open":[197],"new":[198],"avenues":[199],"discovery.":[203]},"counts_by_year":[{"year":2026,"cited_by_count":12}],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2026-01-15T00:00:00"}