{"doi":"10.1101/2020.08.19.257261","title":"Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly","abstract":"ABSTRACT Synaptic vesicle fusion is mediated by membrane-bridging complexes formed by SNARE proteins - VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the pre-synaptic membrane. Accumulating evidence suggest that chaperones Munc18-1 and Munc13-1 co-operatively catalyze SNARE assembly via an intermediate ‘template’ complex containing Syntaxin-1 and VAMP2. How SNAP25 is chaperoned into this nascent complex remains a mystery. Here we report that Munc13-1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single-molecule optical tweezer studies. Detailed structure-function analyses show that the binding is mediated by the Munc13-1 MUN domain and is specific for the SNAP25 ‘linker’ region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and presumably bound in ~1:1 stoichiometry by the self-assembled Munc13-1 nanoclusters. Our data suggests that Munc13-1’s capacity to bind all three synaptic SNARE proteins likely underlie its chaperone function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123960,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331458,"name":"Huaizhou Jin","orcid":"0000-0003-0540-3223","position":1,"is_corresponding":false},{"id":331459,"name":"Feng Li","orcid":"0000-0003-1799-9570","position":2,"is_corresponding":false},{"id":331460,"name":"Tong Shu","orcid":"0000-0001-6036-0057","position":3,"is_corresponding":false},{"id":331461,"name":"Jeff Coleman","orcid":"0000-0003-0110-9289","position":4,"is_corresponding":false},{"id":331462,"name":"Jie Yang","orcid":"0000-0002-3522-0906","position":5,"is_corresponding":false},{"id":331463,"name":"Frédéric Pincet","orcid":"0000-0002-4243-2157","position":6,"is_corresponding":false},{"id":331464,"name":"Yongli Zhang","orcid":"0000-0001-7079-7973","position":7,"is_corresponding":false},{"id":331466,"name":"Shyam S. Krishnakumar","orcid":"0000-0001-6148-3251","position":8,"is_corresponding":false},{"id":331465,"name":"James E. Rothman","orcid":"0000-0003-4822-4161","position":9,"is_corresponding":false},{"id":331457,"name":"Ramalingam Venkat Kalyana Sundaram","orcid":"0000-0002-0232-4186","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}