Table 1.
Binding receptors, amino acids of the metalloprotease active sites, substrate specificity and cleaved peptide bonds of BoNT variants.
| Serotype | Protein Receptor | Ganglioside Receptor | HC-C GBP (SXWY) | Metalloprotease Motif (HExxH) | Substrates | Cleavage Sites |
|---|---|---|---|---|---|---|
| BoNT/A | N-glycosylated SV2A-B-C | GT1b GD1a |
SNWY | HELIH | SNAP-23 | T202–R203 |
| SNAP-25 | Q197–R198 | |||||
| BoNT/B | Synaptotamin-1/2 | GT1b GD1a |
SKWY | HELIH | VAMP-1 | Q78–F79 |
| VAMP-2 | Q76–F77 | |||||
| VAMP-3 | Q63–F64 | |||||
| BoNT/C | none * | GT1b GD1b |
(W)KNY | HELNH | SNAP-25 | R198–A199 |
| Syntaxin-1A,-2,-3 | K253–A254 | |||||
| Syntaxin-1B | K252–A253 | |||||
| BoNT/D | N-glycosylated SV2A-B-C | GT1b GD1b GD2 |
(W)VNY | HELTH | VAMP-1 | K61–L62 |
| VAMP-2 | K59–L60 | |||||
| VAMP-3 | K46–L47 | |||||
| BoNT/DC | Synaptotamin-1/2 | Sialic acid residue | SNYIS | HELTH | VAMP-1 | K61–L62 |
| VAMP-2 | K59–L60 | |||||
| VAMP-3 | K46–L47 | |||||
| BoNT/E | N-glycosylated SV2A-B | GT1b GD1a |
STWY | HELIH | SNAP-23 SNAP-25 |
K185–I186 R180–I181 |
| BoNT/F | N-glycosylated SV2A-B-C | GT1b GD1a |
SSWY | HELIH | VAMP-1 | Q60–K61 |
| VAMP-2 | Q58-K59 | |||||
| VAMP-3 | Q45–K46 | |||||
| BoNT/F5 | Unknown (similar to BoNT/F?) | Unknown (similar to BoNT/F?) | SSWY | HELIH | VAMP-1 | L56–E57 |
| VAMP-2 | L54–E55 | |||||
| VAMP-3 | L41–E42 | |||||
| BoNT/H (BoNT/HA, BoNT/FA) | N-glycosylated SV2C | Unknown (similar to BoNT/A?) | SNWY | HELIH | VAMP-1 | L56–E57 |
| VAMP-2 | L54–E55 | |||||
| VAMP-3 | L41–E42 | |||||
| BoNT/G1 | Synaptotamin-1/2 | GT1b GD1a |
SQWY | HELIH | VAMP-1 | A83–A84 |
| VAMP-2 | A81–A82 | |||||
| VAMP-3 | A68–A69 | |||||
| BoNT/X | Unknown | Unknown | SAWY | HELVH | VAMP-1 | R68–A69 |
| VAMP-2 | R66–A67 | |||||
| VAMP-3 | R53–A54 | |||||
| VAMP-4 | K86–S87 | |||||
| VAMP-5 | R40–S41 | |||||
| Ykt6 | K173–S174 | |||||
| BoNT/Wo | Unknown | Unknown | Not present ** | HEMTH | VAMP-2 | W89–W90 |
| BoNT/En (eBoNT/J) | Unknown | Unknown | SAWY | HELCH | SNAP-25 | K69–D70 |
| VAMP-1 | A69–D70 | |||||
| VAMP-2 | A67–D68 | |||||
| VAMP-3 | A54–D55 | |||||
| Syntaxin-1B | K145–D146 | |||||
| Syntaxin-4 | K191–D192 |
* BoNT/C binding and internalization may be independent from protein receptors. Polysialogangliosides involved in toxin internalization are also indicated. BoNT/DC is unique among BoNTs, not necessarily needing the interaction with polysialogangliosides. BoNT/X and BoNT/En contain the ganglioside binding pocket domain (GBP), but the dual receptor binding process has not been yet proven. ** Conserved residues forming the ganglioside binding pocket (GBP) are not present in the putative binding domain of BoNT/Wo, which may have a different binding mechanism. The enzymatic substrates and cleavage sites experimentally proven are indicated with mouse numbering. SNAP: synaptosomal-associated protein; VAMP: vesicle-associated membrane protein.