Figure 6.

Cartoon illustrating the proposed association between synaptotagmin (gold colored protein) and the SNARE fusion complex (SNAP25, green helix; syntaxin, red helices; and synaptobrevin, blue helix) and the interaction with the phospholipid membrane (yellow plane). Ca⁺² are illustrated as red spheres. The transmembrane anchor of syntaxin and the linker between the H1-H2 domain (red helices to the left of C2A) and the H3 domain of syntaxin (red helices in the SNARE bundle) have been omitted for clarity. In our model, we predict that the Ca⁺²-binding sites of synaptotagmin interact with the presynaptic membrane. The interactions between the SNARE complex and synaptotagmin probably involve the COOH-terminal (membrane-proximal) portion of the SNARE core complex (Kee and Scheller 1996) and the cup-shaped, polybasic regions of the synaptotagmin C2 domains. The association between the NH₂-terminal (H1-H2) domain of syntaxin (red helices to the left of the C2A domain) and the C2A domain of synaptotagmin was modeled according to NMR data (Shao et al. 1997). The peptide distance between the transmembrane domain and the SNARE-binding domain of synaptobrevin (blue helix) is exaggerated in this cartoon.