Sequence alignment of mouse, rat, and human SNAP25 isoforms and cleavage sites of the different BoNTs
The C-terminal SNARE motif of mouse, rat, and human SNAP isoforms have been aligned using http://www.uniprot.org/align/. The conserved cleavage sites targeted by specific BoNT types and subtypes are colored like the respective toxin. Conserved cleavage sites whose susceptibility to cleavage is predicted, but not experimentally proven, are underlined with the color of the respective BoNT. Nonconserved cleavage sites are underlined in black as well as conserved cleavage sites that were experimentally found to be noncleavable. Notice that mouse SNAP-23 has a cleavage site for BoNT/E different from the one present in SNAP-25, which is anyhow cleaved, whereas human SNAP-23, which has the same proteolytic site as SNAP-25, is not cleaved (Vaidyanathan et al., 1999). Similarly, mouse SNAP-23 was reported to be cleaved by BoNT/A, although the peptide bond is not conserved. At the same time, BoNT/C, whose cleavage site is conserved (also in human SNAP-23) does not cleave mouse SNAP-23. The cleavability of rat SNAP-23 was predicted on these premises. When known, the recognition motif used by the toxin to bind the substrate in addition to the cleavage sites (Rossetto et al., 1994) is underlined in red.