alphaSNAP

Alpha-SNAP, also written as alphaSNAP, is a soluble cytosolic protein that plays a central role in the recycling of SNARE proteins after membrane fusion. In humans it is encoded by the NAPA gene. Alpha-SNAP binds to assembled SNARE complexes and, together with the ATPase NSF (N-ethylmaleimide-sensitive factor), drives disassembly of SNARE bundles to regenerate free SNAREs for subsequent rounds of vesicle docking and fusion.

Mechanistically, SNAREs from opposing membranes form a four-helix bundle that mediates vesicle fusion. Following fusion, alpha-SNAP attaches to the SNARE complex and recruits NSF, a hexameric ATPase. ATP hydrolysis by NSF powers disassembly of the SNARE complex, releasing individual SNAREs for reuse in future trafficking events. This disassembly step is essential for maintaining efficient vesicular transport in both secretory and endocytic pathways and is particularly important for rapid synaptic vesicle recycling in neurons.

Alpha-SNAP is widely expressed in eukaryotic cells and is often found in the cytosol with transient association to membranes when SNARE complexes are present. The protein is generally around the 40–50 kDa range in mammals and is predicted to adopt a largely α-helical structure with coiled-coil regions that mediate interactions with SNAREs and NSF. Evolutionarily, alpha-SNAP is conserved across eukaryotes, with Sec17 serving as its functional homolog in yeast.

Clinical and biological significance is tied to proper SNARE recycling; loss or dysfunction of alpha-SNAP disrupts vesicular trafficking and can affect neurotransmitter release and general cellular homeostasis. In many model organisms, alpha-SNAP is essential for viability due to its fundamental role in membrane trafficking.