{"doi":"10.1016/j.jmb.2013.07.001","title":"Subtle Interplay between Synaptotagmin and Complexin Binding to the SNARE Complex","abstract":null,"journal":"Journal of Molecular Biology","year":2013,"id":685215,"datarank":0.5742962094733643,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.0,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":792498,"name":"Kyle D. Brewer","orcid":null,"position":1,"is_corresponding":false},{"id":1790201,"name":"Raquel Perez-Castillejos","orcid":null,"position":2,"is_corresponding":false},{"id":292595,"name":"Josep Rizo","orcid":"0000-0003-1773-8311","position":3,"is_corresponding":false},{"id":828609,"name":"Junjie Xu","orcid":"0000-0003-2914-9514","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Subtle Interplay between Synaptotagmin and Complexin Binding to the SNARE Complex","abstract":"Ca²⁺-triggered neurotransmitter release depends on the formation of SNARE complexes that bring the synaptic vesicle and plasma membranes together, on the Ca²⁺ sensor synaptotagmin-1 and on complexins, which play active and inhibitory roles. Release of the complexin inhibitory activity by binding of synaptotagmin-1 to the SNARE complex, causing complexin displacement, was proposed to trigger exocytosis. However, the validity of this model was questioned based on the observation of simultaneous binding of complexin-I and a fragment containing the synaptotagmin-1 C2 domains (C2AB) to membrane-anchored SNARE complex. Using diverse biophysical techniques, here we show that C2AB and complexin-I do not bind to each other but can indeed bind simultaneously to the SNARE complex in solution. Hence, the SNARE complex contains separate binding sites for both proteins. However, total internal reflection fluorescence microscopy experiments show that C2AB can displace a complexin-I fragment containing its central SNARE-binding helix and an inhibitory helix (Cpx26-83) from membrane-anchored SNARE complex under equilibrium conditions. Interestingly, full-length complexin-I binds more tightly to membrane-anchored SNARE complex than Cpx26-83, and it is not displaced by C2AB. These results show that interactions of N- and/or C-terminal sequences of complexin-I with the SNARE complex and/or phospholipids increase the affinity of complexin-I for the SNARE complex, hindering dissociation induced by C2AB. We propose a model whereby binding of synaptotagmin-1 to the SNARE complex directly or indirectly causes a rearrangement of the complexin-I inhibitory helix without inducing complexin-I dissociation, thus relieving the inhibitory activity and enabling cooperation between synaptotagmin-1 and complexin-I in triggering release.","is_dataset_classified":null,"base_score":3.828641396489095,"endowment":3.828641396489095,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23845424","pmcid":"PMC3786701","openalex_id":"https://openalex.org/W2067463218","authors":[],"funders":[{"funder_name":"Welch Foundation","grant_id":"grant I-1304","title":null},{"funder_name":"National Institutes of Health","grant_id":"grant NS40944","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"NS40944","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS040944","title":null}],"total_grants":4,"fwci":3.044,"citation_percentile":0.90946609,"influential_citations":0,"citation_trend":[{"year":2013,"count":2},{"year":2014,"count":8},{"year":2015,"count":5},{"year":2016,"count":5},{"year":2017,"count":4},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":2},{"year":2021,"count":5},{"year":2022,"count":4},{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0022283613004336?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022283613004336?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jmb.2013.07.001","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23845424","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3786701","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","Lipid Membrane Structure and Behavior","Neuroscience and Neuropharmacology Research","Adaptor Proteins, Vesicular Transport","Animals","Binding, Competitive","Calcium","Cell Membrane","Humans","Multiprotein Complexes","Nerve Tissue Proteins","Osmolar Concentration","Protein Binding","Protein Structure, Secondary","Rats","SNARE Proteins","Solubility","Synaptotagmins"],"mesh_terms":["Animals","Binding, Competitive","Calcium","Cell Membrane","Humans","Nerve Tissue Proteins","Osmolar Concentration","Protein Binding","Solubility","Protein Structure, Secondary","Adaptor Proteins, Vesicular Transport","Multiprotein Complexes","SNARE Proteins","Synaptotagmins","Rats"],"keywords":["Synaptotagmin 1","SNARE complex","Cell biology","Biology","Vesicle fusion","Synaptic vesicle","Exocytosis","Biophysics","Biochemistry","Vesicle","Membrane","Neurotransmitter release","HSQC","HMQC","Tirf","Isothermal Titration Calorimetry","Total Internal Reflection Fluorescence","Itc","Protein–protein Interactions","Synaptic Vesicle Fusion","Protein–membrane Interactions","Tcep","Ca(2+) Triggering","Mals","Trosy","Multiangle Light Scattering","Transverse Relaxation Optimized Spectroscopy","Tris(2-carboxyethyl)phosphine","Heteronuclear Single Quantum Coherence","Heteronuclear Multiple Quantum Coherence"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T16:01:13.556403Z","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":[]}