Figure 6.

Model of a general Ca²⁺–SNARE–synaptotagmin fusion-triggering mechanism. (a) Membrane stalk induced by SNARE complex formation prior to Ca²⁺ arrival between a vesicle (top membrane) and the plasma membrane (bottom membrane). All components are drawn to scale. For details about the generation of the model see Supplementary Methods. Both SNARE-bound and uncomplexed Syt3 molecules residing in the plasma membrane are shown. The model also applies to Syt1 except that the transmembrane domain of Syt1 would reside in the synaptic vesicle. We drew SNARE-bound Syt3 poised to interact with either plasma or synaptic vesicle membrane; it is unknown to which membrane (or both) synaptotagmins bind. Note that in our model simultaneous binding of both complexin and synaptotagmin to SNARE complex is sterically permissible although (partial) competition has been observed in solution¹⁷ (syntaxin–red, synaptobrevin–blue; SNAP25-green; complexin-yellow; synaptotagmin-magenta). Phospholipids are shown as gray cartoons, cholesterol in cyan. (b) Fusion pore after Ca²⁺ (yellow spheres) binding to Syt3. The color code is identical to panel (a). Upon Ca²⁺-influx Syt3 Ca²⁺-binding loops coordinate Ca²⁺ with anionic phospholipids, penetrating the lipid headgroup region⁸, and may induce positive curvature¹⁰.