The two SNARE motifs of SNAP25 are structurally and functionally distinct

The process of intracellular membrane fusion is essential to maintaining eukaryotic membrane and protein homeostasis. The core molecular machinery that catalyzes these events are the SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins, a family of membrane associated or membrane anchored proteins. All SNARE-mediated fusion involves assembly of a coiled helical bundle of four 60–70 residue "SNARE motif" domains that drive membrane fusion. The fusion events involved in synaptic neurotransmitter exocytosis are particularly tightly regulated and driven by a SNARE complex composed of syntaxin-1a and SNAP25 (target membrane or "tSNAREs") on the plasma membrane and synaptobrevin-2 on the vesicle membrane.