User:Enderjh/sandbox

Vesicle fusion is the process of a vesicle approaching a membrane (or another vesicle) and then fusing with it. The SNARE complex, a four-domain complex, is involved in bringing the vesicle in contact with the membrane and bringing about the exocytotic event. Synaptobrevin(VAMP) is bound to the vesicle and contributes one α-helix to the complex while SNAP-25, a Q-SNARE protein, contributes two helices and Syntaxin-1 contributes one helix, both being bound to the plasma membrane. SNAP-25 is a membrane-bound protein anchored to the cytosolic face of membranes via palmitoyl side chains covalently bound to cysteine amino acid residues in the middle of the molecule. This means that SNAP-25 does not contain a trans-membrane domain. SNAP-25 assembles with the other two SNARE complex proteins and the selective binding of these proteins enables vesicle docking and fusion to occur at the correct location.

To form the SNARE complex, the SNARE attached to the vesicle membrane and the two SNARES attached to the plasma membrane associated with each other and begin to wrap around each other and form a coiled coil quarternary structure. The SNARE domains of both synaptobrevin and syntaxin bind to SNAP-25. The two proteins bind to one each of the different SNARE regions on the SNAP-25 protein. Syntaxin binds the α-helix near SNAP-25's N-terminus side while Synaptobrevin binds the c-terminal α-helix.

SNAP-25 inhibits P/Q- and L-type voltage-gated calcium channels located presynaptically and interacts with the synaptotagmin C2B domain in Ca2+-independent fashion. In glutamatergic synapses SNAP-25 decreases the Ca2+ responsiveness, while it is naturally absent in GABAergic synapses.

Two isoforms (mRNA splice variants) of SNAP-25 exist, which are labeled a and b. There are nine amino acid residue differences between the isoforms, including a re-localization of on of the four cysteine residues. . The major characteristics of these two forms are outlined in the table below.