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. 2017 Aug 15;10:256. doi: 10.3389/fnmol.2017.00256

Figure 4.

Figure 4

Energy landscape of the transition from the Munc18-1/syntaxin-1 complex to the ternary SNARE complex in the presence of Munc13-1 and Syt1. (A) Binding of Munc13-1 to the Munc18-1/syntaxin-1 complex induces a conformational rearrangement in the syntaxin-1 linker region (low Gibbs free energy) thus (B) providing a potential nucleation site for N-terminal assembly among syntaxin-1, SNAP-25 and synaptobrevin-2 (metastable state with rather high Gibbs free energy, which is below the energy barrier (black dashed line)); (C) propagation of the four helical SNARE bundle toward the C-terminal end would eventually dissociate the H3 domain of syntaxin-1 from Munc18-1 to reach a stable ternary SNARE complex (extremely low Gibbs free energy). (D) Binding of Syt1 C2B domain to the partially-assembled ternary SNARE complex (metastable state) would help to lower the Gibbs free energy of the total system (gray solid line to gray dashed line), thus stimulating the reaction. Munc18-1, SNAP-25, synaptobrevin-2, Munc13-1, Syt1 C2B domain are colored in purple, green, blue, pink and orange, respectively. Syntaxin-1 is colored in yellow/black/red (yellow: the Habc domain; black: the linker region; red: the H3 domain). The bottom face of Syt1 C2B domain (i.e., R398, R399) is displayed as blue hexagon.