{"doi":"10.1101/2022.01.05.474995","title":"Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand binding specificity","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Somatostatin is a peptide hormone regulating endocrine systems through binding to G-protein-coupled somatostatin receptors. somatostatin receptor 2 (SSTR2) is one of the human somatostatin receptors and highly implicated in cancers and neurological disorders. Here, we report the high resolution cryo-EM structure of full-length human SSTR2 bound to the agonist somatostatin (SST-14) complex with inhibitory G (G\n                  <jats:sub>i</jats:sub>\n                  ) proteins. Our structure shows that seven transmembrane helices form a deep pocket for ligand binding and that the highly conserved Trp-Lys motif of SST-14 positions at the bottom of the pocket. Furthermore, our sequence analysis combined with AlphaFold modeled structures of other SSTR isoforms provide how SSTR family proteins specifically interact with their cognate ligands. This work provides the first glimpse into the molecular recognition of somatostatin receptor and crucial resource to develop therapeutics targeting somatostatin receptors.\n                </jats:p>","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":null,"id":41265,"datarank":0.2267268714953514,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.06193502819513493,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.06193502819513493,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":199017,"name":"Eojin Yoon","orcid":"0000-0003-1480-3384","position":1,"is_corresponding":false},{"id":199018,"name":"Ye-Eun Jeon","orcid":"0000-0002-2667-4375","position":2,"is_corresponding":false},{"id":199019,"name":"Ji-Hye Yun","orcid":"0000-0001-7570-369X","position":3,"is_corresponding":false},{"id":199020,"name":"Naito Ishimoto","orcid":"0000-0001-8976-8582","position":4,"is_corresponding":false},{"id":199021,"name":"Hyeonuk Woo","orcid":"0000-0002-6495-4087","position":5,"is_corresponding":false},{"id":199022,"name":"Sam-Yong Park","orcid":"0000-0001-6164-8896","position":6,"is_corresponding":false},{"id":142344,"name":"Ji-Joon Song","orcid":"0000-0001-7120-6311","position":7,"is_corresponding":false},{"id":119346,"name":"Weontae Lee","orcid":"0000-0003-2347-1262","position":8,"is_corresponding":false},{"id":199016,"name":"Yunseok Heo","orcid":"0000-0002-2233-4306","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18998881","pmcid":null,"openalex_id":"https://openalex.org/W4206509725","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":1,"citation_trend":[{"year":2022,"count":1},{"year":2025,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/01/05/2022.01.05.474995.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/01/05/2022.01.05.474995.full.pdf","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2022/01/05/2022.01.05.474995.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2022.01.05.474995","host_type":"publisher"},{"url":"https://doi.org/10.1101/2022.01.05.474995","host_type":"repository"}],"fields_of_study":["Glycosylation and Glycoproteins Research","Monoclonal and Polyclonal Antibodies Research","Cellular transport and secretion","Biology","Medicine","Chemistry"],"mesh_terms":[],"keywords":["Somatostatin receptor 2","Somatostatin receptor 1","Somatostatin receptor 3","Somatostatin receptor","Somatostatin","Receptor","Agonist","Chemistry","Cell biology","Biochemistry","Biology","Endocrinology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-12T22:52:23.367582Z","pmid":null,"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":[]}