{"doi":"10.1038/s41467-024-54772-3","title":"Fast-diffusing receptor collisions with slow-diffusing peptide ligand assemble the ternary parathyroid hormone–GPCR–arrestin complex","abstract":"Abstract The assembly of a peptide ligand, its receptor, and β-arrestin (βarr) into a ternary complex within the cell membrane is a crucial aspect of G protein-coupled receptor (GPCR) signaling. We explore this assembly by attaching fluorescent moieties to the parathyroid hormone (PTH) type 1 receptor (PTH 1 R), using PTH as a prototypical peptide hormone, along with βarr and clathrin, and recording dual-color single-molecule imaging at the plasma membrane of live cells. Here we show that PTH 1 R exhibits a near-Brownian diffusion, whereas unbound hormone displays limited mobility and slow lateral diffusion at the cell surface. The formation of the PTH–PTH 1 R–βarr complex occurs in three sequential steps: (1) receptor and ligand collisions, (2) phosphoinositide (PIP 3 )-dependent recruitment and conformational change of βarr molecules at the plasma membrane, and (3) collision of most βarr molecules with the ligand-bound receptor within clathrin clusters. Our results elucidate the non-random pathway by which PTH–PTH 1 R–βarr complex is formed and unveil the critical role of PIP 3 in regulating GPCR signaling.","journal":"Nature Communications","year":2024,"id":446068,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":644073,"name":"Karina A. Peña","orcid":"0000-0001-6401-5269","position":1,"is_corresponding":false},{"id":908216,"name":"Sofya Savransky","orcid":"0000-0003-1495-7412","position":2,"is_corresponding":false},{"id":1262866,"name":"Alexandre Gidon","orcid":"0000-0001-9722-1253","position":3,"is_corresponding":false},{"id":245412,"name":"Gerald Hammond","orcid":"0000-0002-6660-3272","position":4,"is_corresponding":false},{"id":690841,"name":"John Janetzko","orcid":"0000-0003-1604-2515","position":5,"is_corresponding":false},{"id":281860,"name":"Jean‐Pierre Vilardaga","orcid":"0000-0002-1217-1435","position":6,"is_corresponding":false},{"id":418055,"name":"Jonathan Pacheco","orcid":"0000-0001-6880-5874","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:01:50.465308Z","pmid":"39627206","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":[]}