Question

SNARE helical motifs share a universal length (~60 amino acids). The N’ to C’ terminal zippering to form a highly stable four-helical bundle is thought to provide the energy to fuse membranes. First principles suggest that a longer SNARE four helical bundle would provide greater fusion energy per SNARE bundle, necessitating fewer SNAREs for each membrane fusion. However, families of longer SNAREs (e.g., 120 or 180 amino acids) are unknown. Suggest a possible rationale for why longer SNAREs don’t co-exist with our common ~60 amino acid SNARE motifs.

Answer 1

Most of the SNAREs are small amino acid peptides. The most discussed and well-known SNAREs are brevins, syntaxin, etc. They almost have the same structural configurations. They form a very stable complex by forming a bundle of four parallel alpha residues and the SNARE-induced lateral tension caused by the zippering of the complex, causes the membrane breakdown leading to the formation of the fusion pore.

But, there are some long SNAREs also, such as longins. These SNAREs have the same functional mechanism.

But the only difference lies in their N-terminal region. Where small SNAREs possess small alpha-helices in their N-terminal end, the longer SNAREs have alpha-beta-alpha sandwich domains in their N-terminal end. The N-terminal part of the SNAREs regulates the assembly of the coiled-coil domain and thus membrane fusion. So, irrespective of having a similar coiled-coil structure to form the four-helical bundle structure, the difference in the regulation of the activity of the small and long SNAREs can lead to the non-coexistence of them. So, either the common SNAREs function or the long SNAREs. But it is quite hard to expect them to function together at the same location.