title: Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion.
abstract: Synaptotagmin-1 (Syt1) acts as a Ca(2+) sensor for neurotransmitter release through its C2 domains. It has been proposed that Syt1 promotes SNARE-dependent fusion mainly through its C2B domain, but the underlying mechanism is poorly understood. In this study, we show that the C2B domain interacts simultaneously with acidic membranes and SNARE complexes via the top Ca(2+)-binding loops, the side polybasic patch, and the bottom face in response to Ca(2+). Disruption of the simultaneous interactions completely abrogates the triggering activity of the C2B domain in liposome fusion. We hypothesize that the simultaneous interactions endow the C2B domain with an ability to deform local membranes, and this membrane-deformation activity might underlie the functional significance of the Syt1 C2B domain in vivo.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shen
authors.identifier: 0000-0002-5013-1039
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Cong
authors.identifier: 0000-0002-7814-0500
authors.initials: C
authors.lastname: Ma
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion; D008566:Membranes / Q000378:metabolism*; D000072417:Protein Domains; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism*; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism*
chemical_list: D008081:Liposomes; D011994:Recombinant Proteins; D050600:SNARE Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D002118:Calcium
keywords: E. coli; biophysics; exocytosis; mouse; neuroscience; neurotransmitter release; rat; structural biology; synaptic vesicle fusion