{"doi":"10.1126/sciadv.adx5831","title":"A nut-and-bolt assembly of the bimodular large progenitor botulinum neurotoxin complex","abstract":"Botulinum neurotoxin serotype A (BoNT/A) is naturally produced by bacteria along with four nontoxic neurotoxin-associated proteins (NTNH, HA70, HA33, and HA17), forming a bimodular large progenitor toxin complex (L-PTC). The BoNT/A-NTNH complex protects the toxin from adverse environment, while the complex consisting of HA proteins facilitates toxin absorption during oral intoxication. How these two independent modules assemble into the L-PTC remains unclear. Here, we report the crystal structure of the BoNT/A-NTNH-HA70 complex at ~2.9-Å resolution. The structure reveals that the BoNT/A-NTNH complex is anchored into a concentric double β-barrel channel of trimeric HA70 through a short β-hairpin of NTNH (termed nLoop), resembling a nut-and-bolt attachment. We find that the nLoop of NTNH is strictly conserved across HA-containing BoNT complexes and that NTNH-HA70 binding is interchangeable among them. Furthermore, we demonstrate that the nLoop functions as a minimal motif enabling attachment of a protein-of-interest to the HA complex, with potential applications in oral biologics delivery.","journal":"Science Advances","year":2025,"id":528748,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247167,"name":"Linfeng Gao","orcid":"0000-0001-6194-5145","position":1,"is_corresponding":false},{"id":1062225,"name":"Adina Przykopanski","orcid":null,"position":2,"is_corresponding":false},{"id":891763,"name":"Baohua Chen","orcid":"0000-0002-8859-2762","position":3,"is_corresponding":false},{"id":1368122,"name":"Ting Huang","orcid":"0000-0001-7493-9916","position":4,"is_corresponding":false},{"id":712897,"name":"Maren Krüger","orcid":"0000-0001-9775-3110","position":5,"is_corresponding":false},{"id":1407503,"name":"Anna-Magdalena Bartels","orcid":null,"position":6,"is_corresponding":false},{"id":1088832,"name":"Martin B. Dorner","orcid":"0000-0002-8176-797X","position":7,"is_corresponding":false},{"id":373858,"name":"Kay Perry","orcid":"0000-0002-4046-1704","position":8,"is_corresponding":false},{"id":424624,"name":"Brigitte G. Dorner","orcid":"0000-0002-5100-2546","position":9,"is_corresponding":false},{"id":1061627,"name":"Andreas Rummel","orcid":"0000-0002-0645-1641","position":10,"is_corresponding":false},{"id":373860,"name":"Rongsheng Jin","orcid":"0000-0003-0348-7363","position":11,"is_corresponding":false},{"id":373857,"name":"Kwok Ho Lam","orcid":"0000-0002-7173-6600","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:50:52.565868Z","pmid":"40864694","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":[]}