Figure 7. Interplay between the Interactions of Munc13–1, α-RIM, and Rab3s.

(A) Structures of the Munc13–1 C ₂A-domain homodimer and the Munc13–1 _3–150(K32E)/RIM2α _82–142 heterodimer superimposed using monomer C of the homodimer (green) and monomer A of the heterodimer (orange). Ribbon diagrams and transparent surface representations are shown for monomer A of the homodimer (red) and RIM2α _82–142 (blue) to illustrate the steric clash that would occur if both complexes co-existed. The K99 side chain of the ZF domain is shown as a space-filling model. The inset shows a close-up of the region where this side chain (shown here as stick model) would insert into the homodimer interface (the surface representations are not shown).

(B) Structures of the Munc13–1 _3–150(K32E)/RIM2α _82–142 heterodimer and the rabphilin/Rab3A complex [ 27] superimposed using the ZF domains of RIM2α (blue) and rabphilin (green). Ribbon diagrams and transparent surface representations are shown for Munc13–1 _3–150(K32E) (orange) and Rab3A (purple). Zinc atoms are shown as yellow (RIM2α) or red (rabphilin) spheres. The SGAWFF motif of rabphilin is shown as cyan stick model.

(C) Model of a cascade of protein–protein interactions that may regulate synaptic vesicle priming and presynaptic plasticity. Munc13–1 is shown in orange and Rab3 in purple. α-RIM is shown in blue (ZF domain), green (helices a1 and a2), and red (SGAWFY motif). The model represents how formation of the tripartite Munc13–1/α-RIM/Rab3 complex involves dissociation of the Munc13–1 homodimer and release of the interaction between the SGAWFY motif and Rab3A.