{"doi":"10.7554/elife.57154","title":"Ca2+-dependent release of synaptotagmin-1 from the SNARE complex on phosphatidylinositol 4,5-bisphosphate-containing membranes","abstract":"The Ca 2+ sensor synaptotagmin-1 and the SNARE complex cooperate to trigger neurotransmitter release. Structural studies elucidated three distinct synaptotagmin-1-SNARE complex binding modes involving ‘polybasic’, ‘primary’ and ‘tripartite’ interfaces of synaptotagmin-1. We investigated these interactions using NMR and fluorescence spectroscopy. Synaptotagmin-1 binds to the SNARE complex through the polybasic and primary interfaces in solution. Ca 2+ -free synaptotagmin-1 binds to SNARE complexes anchored on PIP 2 -containing nanodiscs. R398Q/R399Q and E295A/Y338W mutations at the primary interface, which strongly impair neurotransmitter release, disrupt and enhance synaptotagmin-1-SNARE complex binding, respectively. Ca 2+ induces tight binding of synaptotagmin-1 to PIP 2 -containing nanodiscs, disrupting synaptotagmin-1-SNARE interactions. Specific effects of mutations in the polybasic region on Ca 2+ -dependent synaptotagmin-1-PIP 2 -membrane interactions correlate with their effects on release. Our data suggest that synaptotagmin-1 binds to the SNARE complex through the primary interface and that Ca 2+ releases this interaction, inducing PIP 2 /membrane binding and allowing cooperation between synaptotagmin-1 and the SNAREs in membrane fusion to trigger release.","journal":"eLife","year":2020,"id":56350,"datarank":2.4302550961616514,"base_score":4.465908118654584,"endowment":4.465908118654584,"self_citation_contribution":0.6698862177981877,"citation_network_contribution":1.7603688783634637,"self_endowment_contribution":0.6698862177981877,"citer_contribution":1.7603688783634637,"corpus_percentile":null,"corpus_rank":null,"citation_count":86,"citer_count":70,"citers_with_citation_signal":52,"citers_with_endowment":52,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":true,"deposit_databanks":{"Dryad":["10.5061/dryad.0zpc866vt"]},"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":292594,"name":"Klaudia Jaczynska","orcid":"0000-0003-2113-2320","position":1,"is_corresponding":false},{"id":292595,"name":"Josep Rizo","orcid":"0000-0003-1773-8311","position":2,"is_corresponding":false},{"id":292593,"name":"Rashmi Voleti","orcid":"0000-0002-3705-7460","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T21:05:49.581291Z","pmid":"32808925","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":[]}