{"doi":"10.1016/j.celrep.2023.113173","title":"Rules and mechanisms governing G protein coupling selectivity of GPCRs","abstract":"G protein-coupled receptors (GPCRs) convert extracellular stimuli into intracellular signaling by coupling to heterotrimeric G proteins of four classes: G i/o , G q , G s , and G 12/13 . However, our understanding of the G protein selectivity of GPCRs is incomplete. Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G 12/13 -coupled receptor, G 15 -coupled receptors, and a variety of subclasses for G i/o -, G q -, and G s -coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. We further identify the structural determinants of G protein selectivity, allowing us to synthesize non-existent GPCRs with de novo G protein selectivity and efficiently identify putative pathogenic variants.","journal":"Cell Reports","year":2023,"id":316995,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":87,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":811567,"name":"Ryoji Kise","orcid":"0009-0000-6583-1719","position":1,"is_corresponding":false},{"id":583209,"name":"Pablo Gaínza","orcid":"0000-0001-9197-0982","position":2,"is_corresponding":false},{"id":670974,"name":"Ee Von Moo","orcid":"0000-0003-2629-9779","position":3,"is_corresponding":false},{"id":1021546,"name":"Xiaona Li","orcid":"0000-0002-7041-2604","position":4,"is_corresponding":false},{"id":1021547,"name":"Ryosuke Tany","orcid":"0000-0003-3002-1833","position":5,"is_corresponding":false},{"id":1022114,"name":"Hideko Wakasugi-Masuho","orcid":null,"position":6,"is_corresponding":false},{"id":655137,"name":"Bruno E. Correia","orcid":"0000-0002-7377-8636","position":7,"is_corresponding":false},{"id":392553,"name":"Kirill A. Martemyanov","orcid":"0000-0002-9925-7599","position":8,"is_corresponding":false},{"id":254633,"name":"Ikuo Masuho","orcid":"0000-0001-8754-987X","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:06:44.698773Z","pmid":"37742189","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}