{"doi":"10.1371/journal.pbio.3002217","title":"A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3","abstract":"Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins.","journal":"PLoS Biology","year":2023,"id":357475,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9546,"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":831988,"name":"Paula Flórez Salcedo","orcid":"0000-0002-2109-8612","position":1,"is_corresponding":false},{"id":1107281,"name":"Emilie Mueller","orcid":null,"position":2,"is_corresponding":false},{"id":831987,"name":"Thomas Lund Koch","orcid":"0000-0002-8489-0375","position":3,"is_corresponding":false},{"id":1107282,"name":"Lau D. Kjelgaard","orcid":null,"position":4,"is_corresponding":false},{"id":502778,"name":"Maren Watkins","orcid":"0000-0002-4127-1961","position":5,"is_corresponding":false},{"id":1047870,"name":"Linda G. Zachariassen","orcid":null,"position":6,"is_corresponding":false},{"id":1106941,"name":"Pernille Sønderby Tuelung","orcid":"0000-0002-0879-5675","position":7,"is_corresponding":false},{"id":930985,"name":"Jeffrey R. McArthur","orcid":"0000-0002-2546-7913","position":8,"is_corresponding":false},{"id":930986,"name":"David J. Adams","orcid":"0000-0002-7030-2288","position":9,"is_corresponding":false},{"id":54802,"name":"Anders S. Kristensen","orcid":"0000-0001-8955-6790","position":10,"is_corresponding":false},{"id":356824,"name":"Baldomero M. Olivera","orcid":"0000-0003-4556-1410","position":11,"is_corresponding":false},{"id":773513,"name":"Rocio K. Finol‐Urdaneta","orcid":"0000-0003-2157-4532","position":12,"is_corresponding":false},{"id":356826,"name":"Helena Safavi-­Hemami","orcid":"0000-0002-1984-2721","position":13,"is_corresponding":false},{"id":1106942,"name":"Jens Preben Morth","orcid":"0000-0003-4077-0192","position":14,"is_corresponding":false},{"id":356825,"name":"Lars Ellgaard","orcid":"0000-0002-7018-0137","position":15,"is_corresponding":false},{"id":1106940,"name":"Celeste Menuet Hackney","orcid":"0000-0002-3009-0495","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T01:13:34.795336Z","pmid":"37535677","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":[]}