Extended Data Fig. 10: Syt1 is predicted to bind to the N-terminal region of SV2A and binding of various ligands to SV2A and the SV2A-Syt1 complex.
From: Structures of synaptic vesicle protein 2A and 2B bound to anticonvulsants
a. The AlphaFold predicted SV2A structure (grey) was aligned to the experimental SV2A structure (dark blue) and cryoEM density (transparent grey). The C2B domain crystal structure (PDB: 4V11) of Syt1 (cyan) with bound SV2A peptide was aligned to the AlphaFold predicted structure. The AlphaFold predicted structure of Syt1 (tan) was also aligned to the C2B Syt1 crystal structure. b. The SV2B experimental structure (dark blue) was aligned to the AlphaFold predicted structure (grey) and the cryoEM density (transparent grey). c. Binding of UCB-J to SV2A (black curve, Kd = 3.7 ± 1.4 nM) or SV2A-Syt1 complex (red curve, Kd = 4.7 ± 1.8 nM). d. Binding of PSL to SV2A (black curve, Kd = 35 ± 3 nM) or SV2A-Syt1 complex (red curve, Kd = 30 ± 4 nM). e. Competition binding of LEV to SV2A (black curve, Ki = 4.4 ± .7 µM) or SV2A-Syt1 complex (red curve, Ki = 3.4 ± .7 µM). f. Competition binding of BRV to SV2A (black curve, Ki = 317 ± 55 nM) or SV2A-Syt1 complex (red curve, Ki = 353 ± 204 nM). Data shown in panels c-f are shown as mean ± s.e.m., exact values, the number of repeated independent experiments are reported in Supplementary Table 4.
