{"doi":"10.1038/s42004-024-01262-8","title":"Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein","abstract":"Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces.","journal":"Communications Chemistry","year":2024,"id":435648,"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":0.9567,"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":1046623,"name":"Jana Škerlová","orcid":"0000-0002-9579-4047","position":1,"is_corresponding":false},{"id":645969,"name":"Pyung‐Gang Lee","orcid":"0000-0001-9895-1098","position":2,"is_corresponding":false},{"id":270543,"name":"Jie Zhang","orcid":"0009-0009-6965-5607","position":3,"is_corresponding":false},{"id":1243247,"name":"Ajda Krč","orcid":"0009-0007-5842-8527","position":4,"is_corresponding":false},{"id":1058637,"name":"Abhishek Sirohiwal","orcid":"0000-0002-4073-7627","position":5,"is_corresponding":false},{"id":1163931,"name":"Dave Burgin","orcid":null,"position":6,"is_corresponding":false},{"id":1163503,"name":"Mark Elliott","orcid":"0000-0002-5281-7245","position":7,"is_corresponding":false},{"id":1163932,"name":"Jules Philippe","orcid":null,"position":8,"is_corresponding":false},{"id":1163504,"name":"Sarah Donald","orcid":"0000-0002-7189-3200","position":9,"is_corresponding":false},{"id":1163933,"name":"Fraser Hornby","orcid":null,"position":10,"is_corresponding":false},{"id":1163934,"name":"Linda Henriksson","orcid":null,"position":11,"is_corresponding":false},{"id":493674,"name":"Geoffrey Masuyer","orcid":"0000-0002-9527-2310","position":12,"is_corresponding":false},{"id":911120,"name":"Ville R. I. Kaila","orcid":"0000-0003-4464-6324","position":13,"is_corresponding":false},{"id":1163505,"name":"Matthew Beard","orcid":"0000-0003-3249-7851","position":14,"is_corresponding":false},{"id":298483,"name":"Min Dong","orcid":"0000-0002-1744-7293","position":15,"is_corresponding":false},{"id":262398,"name":"Pål Stenmark","orcid":"0000-0003-4777-3417","position":16,"is_corresponding":false},{"id":1163502,"name":"Markel Martínez‐Carranza","orcid":"0000-0003-0192-9762","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:00:08.103086Z","pmid":"39138288","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":[]}