{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Makke M"],"funding":["Deutsche Forschungsgemeinschaft"],"pagination":["RP92438"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11589869"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["Complexin determines magnitude and kinetics of synchronized secretion, but the underlying molecular mechanisms remained unclear. Here, we show that the hydrophobic face of the amphipathic helix at the C-terminus of Complexin II (CpxII, amino acids 115-134) binds to fusion-promoting SNARE proteins, prevents premature secretion, and allows vesicles to accumulate in a release-ready state in mouse chromaffin cells. Specifically, we demonstrate that an unrelated amphipathic helix functionally substitutes for the C-terminal domain (CTD) of CpxII and that amino acid substitutions on the hydrophobic side compromise the arrest of the pre-fusion intermediate. To facilitate synchronous vesicle fusion, the N-terminal domain (NTD) of CpxII (amino acids 1-27) specifically cooperates with synaptotagmin I"],"journal":["eLife"],"pubmed_title":["Key determinants of the dual clamp/activator function of Complexin."],"pmcid":["PMC11589869"],"funding_grant_id":["CRC 1027"],"pubmed_authors":["Pastor-Ruiz A","Gaya S","Makke M","Bruns D","Yarzagaray A","Frisch W","Zimmer M"],"additional_accession":[]},"is_claimable":false,"name":"Key determinants of the dual clamp/activator function of Complexin.","description":"Complexin determines magnitude and kinetics of synchronized secretion, but the underlying molecular mechanisms remained unclear. Here, we show that the hydrophobic face of the amphipathic helix at the C-terminus of Complexin II (CpxII, amino acids 115-134) binds to fusion-promoting SNARE proteins, prevents premature secretion, and allows vesicles to accumulate in a release-ready state in mouse chromaffin cells. Specifically, we demonstrate that an unrelated amphipathic helix functionally substitutes for the C-terminal domain (CTD) of CpxII and that amino acid substitutions on the hydrophobic side compromise the arrest of the pre-fusion intermediate. To facilitate synchronous vesicle fusion, the N-terminal domain (NTD) of CpxII (amino acids 1-27) specifically cooperates with synaptotagmin I","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-03T07:25:47.379Z","creation":"2025-04-04T02:33:25.32Z"},"accession":"S-EPMC11589869","cross_references":{"pubmed":["39585326"],"doi":["10.7554/eLife.92438"]}}