A Autoinhibition of the Munc18-1/Syx1 complex. The closed Syx1 linker region and the bent Munc18-1 domain 3a render this complex inactivate, inhibiting Syx1 association with SN25 and Syb2. B Activation of the Munc18-1/Syx1 complex by Munc13 MUN domain. The MUN domain catalyzes opening of the Syx1 linker region via binding to H11 of domain 3a and Syx1 linker region, leading to a conformational flexibility of domain 3a (between bend and extension). The open Syx1 linker region and putative unstructured N-terminal of Syx1-H3 are displayed by lemon green and blue dashed lines, respectively. C Templating function of domain 3a. Assisted with Munc13 MUN domain, the extended domain 3a serves as a template for Syx1-H3 and Syb2 simultaneously, awaiting SN25 entry and registering SNARE complex assembly at the N-terminus. Dashed lines indicate putative unstructured regions. D SNARE complex assembly. Proceeding of SNARE four-helix bundle inside the central cavity of Munc18-1 to complete SNARE complex formation and membrane fusion. 