Practice question

Final step of vesicular traffic requires merging of two lipid bilayers normally separated by hydration repulsion and electrostatic forces. SNARE proteins provide mechanical work through formation of extremely stable coiled-coil bundle. Vesicle-anchored R-SNAREs like VAMP2/synaptobrevin carry single SNARE motif with arginine at ionic layer, while target membrane Q-SNAREs syntaxin-1 and SNAP-25 contribute three motifs with glutamine at ionic layer; together they zipper progressively from membrane-distal N termini toward membrane-proximal C termini into parallel four-helix bundle releasing energy sufficient to pull membranes within one to two nanometers, inducing hemifusion stalk and fusion pore opening. Regulatory SM proteins such as Munc18, Munc13 and complexin, plus Rab effectors and tethering complexes like exocyst and HOPS, ensure correct pairing and timing before full zippering. After fusion, resulting cis-SNARE complex is disassembled by hexameric AAA ATPase NSF and adaptor α-SNAP using ATP hydrolysis for reuse. This engine underlies ER-Golgi transport, endosomal trafficking and synaptic neurotransmitter release, distinct from nuclear import, cargo selection or proteolysis, and mutations cause neurological and immunological disorders affecting membrane merging pathways.