{"doi":"10.1101/2023.08.29.555158","title":"Step-wise activation of a Family C GPCR","abstract":"Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging we reveal distinct receptor conformations upon allosteric modulator and G protein binding.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393585,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":644199,"name":"Haoqing Wang","orcid":"0000-0003-0277-3018","position":1,"is_corresponding":false},{"id":712155,"name":"Chris Habrian","orcid":null,"position":2,"is_corresponding":false},{"id":239849,"name":"Naomi R. Latorraca","orcid":"0000-0002-8310-8708","position":3,"is_corresponding":false},{"id":345528,"name":"Jun Xu","orcid":"0000-0002-1600-583X","position":4,"is_corresponding":false},{"id":255548,"name":"Evan S. O’Brien","orcid":"0000-0002-2260-7722","position":5,"is_corresponding":false},{"id":732737,"name":"Chen‐Song Zhang","orcid":"0000-0001-5218-0101","position":6,"is_corresponding":false},{"id":693237,"name":"Elizabeth Montabana","orcid":null,"position":7,"is_corresponding":false},{"id":353030,"name":"Antoine Koehl","orcid":"0000-0003-2367-1096","position":8,"is_corresponding":false},{"id":478687,"name":"Susan Marqusee","orcid":"0000-0001-7648-2163","position":9,"is_corresponding":false},{"id":292946,"name":"Ehud Y. Isacoff","orcid":"0000-0003-4775-9359","position":10,"is_corresponding":false},{"id":251465,"name":"Brian K. Kobilka","orcid":"0000-0001-5958-3990","position":11,"is_corresponding":false},{"id":255546,"name":"Kaavya Krishna Kumar","orcid":"0000-0003-2283-4033","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37693614","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":[]}