(a, c) Schematics of different C2 binding and membrane tethering states of E-Syt1 (a) or E-Syt2 (c) in the absence and presence of Ca2+. (b, d) Calculated probabilities (top panel), tethering force (middle), and total free energy (bottom) of different states of E-Syt1 (b) or E-Syt2 (d). Calculations corresponding to the presence of Ca2+ or the absence of Ca2+ are indicated by solid and dashed lines, respectively. Equilibrium states are indicated by filled circles with their sizes representing the corresponding state probabilities.