Membrane Fusion: Role of SNAREs and Calcium

Life processes are governed at the chemical level, and therefore knowledge of how single molecules interact, provides a fundamental understanding of nature. The molecular mechanism of membrane fusion essential to vital cellular activities such as intracellular transport, hormone secretion, enzyme release, or neurotransmission, involve the assembly and disassembly of a specialized set of proteins present in opposing bilayers. Target membrane proteins at the cell plasma membrane SNAP-25 and syntaxin termed t-SNAREs, and secretory vesicle-associated protein VAMP or v-SNARE, are part of the conserved protein complex involved in fusion of opposing membranes. It has been demonstrated that in the presence of Ca2+, t-SNAREs and v-SNARE in opposing bilayers interact and self-assemble in a circular pattern, to form conducting channels. Such self-assembly of t-/v-SNAREs in a ring conformation occurs only when the respective SNAREs are in association with membrane. X-ray diffraction measurements further demonstrate that t-SNAREs in the target membrane and v-SNARE in the vesicle membrane overcome repulsive forces to bring opposing membranes close to within a distance of 2.8 Å. Studies suggest that calcium bridging of the opposing bilayers, lead to release of water from hydrated Ca2+ ions as well as the loosely coordinated water at PO-lipid head groups, leading to membrane destabilization and fusion. The t-/v-SNARE is a tight complex, who's disassembly requires an ATPase called NSF, which functions as a right-handed molecular motor.