{"doi":"10.1101/2024.01.26.577439","title":"Structure of the extracellular region of the adhesion GPCR CELSR1 reveals a compact module which regulates G protein-coupling","abstract":"Abstract Cadherin EGF Laminin G seven-pass G-type receptors (CELSRs or ADGRCs) are conserved adhesion G protein-coupled receptors which are essential for animal development. CELSRs have extracellular regions (ECRs) containing 23 adhesion domains which couple adhesion to intracellular signaling. However, molecular-level insight into CELSR function is sparsely available. We report the 4.3 Å cryo-EM reconstruction of the mCELSR1 ECR with 13 domains resolved in the structure. These domains form a compact module mediated by interdomain interactions with contact between the N- and C-terminal domains. We show the mCELSR1 ECR forms an extended species in the presence of Ca 2+ , which we propose represents the antiparallel cadherin repeat dimer. Using assays for adhesion and G protein-coupling, we assign the N-terminal CADH1-8 module as necessary for cell adhesion and we show the C-terminal CAHD9-GAIN module regulates signaling. Our work provides important molecular context to the literature on CELSR function and opens the door towards further mechanistic studies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484248,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"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":1325899,"name":"Krassimira Garbett","orcid":"0000-0003-3969-3919","position":1,"is_corresponding":false},{"id":1041793,"name":"Szymon P. Kordon","orcid":"0000-0002-3770-0743","position":2,"is_corresponding":false},{"id":1325900,"name":"Ethan Dintzner","orcid":"0009-0003-4821-2766","position":3,"is_corresponding":false},{"id":1325901,"name":"Tanner Shearer","orcid":"0000-0001-5692-7102","position":4,"is_corresponding":false},{"id":720343,"name":"Richard Sando","orcid":"0000-0002-1797-2346","position":5,"is_corresponding":false},{"id":342827,"name":"Demet Araç","orcid":"0000-0002-5444-5799","position":6,"is_corresponding":false},{"id":958402,"name":"Sumit J. Bandekar","orcid":"0000-0003-2728-7366","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T02:07:38.055693Z","pmid":"38328199","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":[]}