Botulinum toxin causes flaccid paralysis by inhibiting neurotransmitter (acetylcholine) release from the presynaptic membranes of nerve terminals of the eukaryotic host skeletal and autonomic nervous system, with frequent heart or respiratory failure. Precursor of botulinum neurotoxin B which has 2 coreceptors; complex polysialylated gangliosides found on neural tissue and specific membrane-anchored proteins found in synaptic vesicles (PubMed:17185412, PubMed:17167421, PubMed:17167418, PubMed:23807078). Receptor proteins are exposed on host presynaptic cell membrane during neurotransmitter release, when the toxin heavy chain (HC) binds to them (PubMed:14504267). Upon synaptic vesicle recycling the toxin is taken up via the endocytic pathway (PubMed:14504267). When the pH of the toxin-containing endosome drops a structural rearrangement occurs so that the N-terminus of the HC forms pores that allows the light chain (LC) to translocate into the cytosol (PubMed:3856850). Once in the cytosol the disulfide bond linking the 2 subunits is reduced and LC cleaves its target protein on synaptic vesicles, preventing their fusion with the cytoplasmic membrane and thus neurotransmitter release. Binds to host peripheral neuronal presynaptic membranes via synaptotagmins 1 and 2 (SYT1 and SYT2) (PubMed:8144634, PubMed:14504267). Toxin binds to the membrane proximal extra-cytoplasmic region of host SYT1 and SYT2 that is transiently exposed outside of cells during exocytosis; exogenous gangliosides enhance binding and subsequent uptake of toxin into host cells (PubMed:14504267, PubMed:15123599). Toxin uptake into neural cells requires stimulation (incubation with K(+) to stimulate SYT protein receptor exposure); subsequently the toxin colocalizes with its receptor in host cells with a concomitant decrease in target protein (synaptobrevin-2/VAMP2) immunoreactivity (PubMed:14504267). Toxin uptake can be blocked by the appropriate synaptotagmin protein fragments and gangliosides in cell culture and in mice (PubMed:14504267, PubMed:15123599). BoNT/B is a 'coincidence detector'; it requires simultaneous binding to coreceptor GT1b and low pH to transform into a membrane-bound, oligomeric channel (PubMed:21925111, PubMed:22720883). Whole toxin only has protease activity after reduction which releases LC (PubMed:1331807, PubMed:7803399). Has proteolytic activity (PubMed:1331807). After translocation into the eukaryotic host cytosol, inhibits neurotransmitter release by acting as a zinc endopeptidase that cleaves the '76-Gln-|-Phe-77' bond of synaptobrevin-2/VAMP2, blocking neurotransmitter release (PubMed:1331807, PubMed:7803399). In vitro the LC only has protease activity after reduction (PubMed:1331807, PubMed:7803399). Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol. Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The N-terminus of the TD wraps an extended belt around the perimeter of the LC; it does not seem to protect the active site, but might prevent premature LC dissociation from the translocation channel and protect toxin prior to translocation (PubMed:10932256, PubMed:17167418). Has 2 coreceptors; complex gangliosides found primarily on neural tissue and host synaptotagmin-1 and -2 (SYT1 and SYT2) which bind simultaneously to adjacent but separate sites at the tip of the HC (PubMed:8144634, PubMed:17185412, PubMed:17167421, PubMed:17167418, PubMed:23807078). HC alone partially prevents uptake of whole toxin by neural cells, and delays paralysis onset by 160% (PubMed:10413679). Binding probably positions the TD for integration into the synaptic vesicle membrane (PubMed:17167418, PubMed:23807078). The HC forms channels at low pH that mediate transport of the light chain (LC) from the endocytic vesicle to the cytosol (PubMed:3856850). Binds gangliosides GD1b and GT1b (PubMed:10413679, PubMed:14731268). Gangliosides are not only a coreceptor, but also required for uptake into nerve cells (PubMed:21925111, PubMed:17167418). HC alone binds to host receptor proteins SYT1 and SYT2 (PubMed:14504267, PubMed:15123599, PubMed:17185412, PubMed:19650874). Interaction with SYT1 protein does not require SYT1 glycosylation (PubMed:19476346). The HC C-terminus (approximately residues 1079-1291) interacts with host SYT2 (PubMed:15123599, PubMed:17167421, PubMed:17167418, PubMed:23807078). Has higher affinity for SYT2 than SYT1 (PubMed:17185412, PubMed:17167421). Significantly decreases uptake and toxicity of whole BoNT/B and BoNT/G (PubMed:19650874). Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on small molecule substrates. Binds 1 zinc ion per subunit, to the LC (PubMed:1429690, PubMed:10932256, PubMed:17167418). Proteolysis inhibited by EDTA and captopril, and by peptides that encompass the VAMP2 cleavage site (Ala-Ser-Gln-Phe-Glu-Thr-Ser and Gln-Phe-Glu-Thr) (PubMed:1331807). Translocation of whole toxin into neurons is inhibited by toosendanin (PubMed:21925111). kcat is 3.96, 4.68 and 3.50 sec(-1) for over-expressed human VAMP1, VAMP2 and VAMP3 respectively. Heterodimer; disulfide-linked heterodimer of a light chain (LC) and a heavy chain (HC) (PubMed:3139097, PubMed:1331807). At pH 4.4 in the presence of ganglioside GT1b may form trimers (PubMed:21925111, PubMed:22720883). Interacts with host receptor synaptotagmin-1 (SYT1); interaction is improved in the presence of gangliosides (PubMed:8144634, PubMed:14504267, PubMed:19650874). Interacts with host receptor synaptotagmin-2 (SYT2) (PubMed:14504267, PubMed:15123599, PubMed:19650874, PubMed:17167421, PubMed:17167418, PubMed:23807078). SYT2 interaction and toxin uptake do not require gangliosides but are improved in their presence (PubMed:14504267, PubMed:15123599). HC interacts with a complex including at least host synaptic vesicle glycoprotein 2 (SV2) and synaptotagmin-1 (SYT1); copurification does not depend on glycosylation of either protein (PubMed:19476346). Colocalizes with its SYT1 receptor, probably in synaptic vesicles (PubMed:14504267). At pH 4.4 in the presence of ganglioside GT1b becomes a membrane-associated hydrophobic protein (PubMed:21925111). Has protease activity (PubMed:1331807). Has 3 functional domains; the translocation domain (TD) and the receptor-binding domain (RBD) which is further subdivided into N- and C-terminal domains (N-RBD and C-RBD) (PubMed:10932256). HC forms channels in bilayers at low pH (PubMed:3856850). The N-terminal belt of the TD wraps an extended belt around the perimeter of the LC; it is shorter than in BoNT/A and does not block the active site (PubMed:10932256). The belt may be a pseudosubstrate inhibitor which serves as an intramolecular chaperone for the LC prior to its translocation into the host cytosol (PubMed:17907800). Available under the name MYOBLOC (rimabotulinumtoxinB, US WorldMeds, LLC) for the treatment of adults with cervical dystonia. There are seven antigenically distinct forms of botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are quite frequent. Botulism poisoning is usually food-borne, either by ingesting toxin or bacterial-contaminated food, or less frequently by inhalation poisoning. In both cases the neurotoxin binds to the apical surface of epithelial cells in the gut or airway. Toxin undergoes receptor-mediated endocytosis (using a different receptor than on target nerve cells), transcytosis across the epithelial cells and release into the general circulation. Once in the general circulation it binds to its target cells. Types A, B and E are the most frequent cause of adult human foodborne botulism; type A is the most severe, while type E has the shortest incubation period (PubMed:1431246). Neurotoxin type B is released from bacteria mostly as a single chain and cleaved by host proteases into the active dichain (PubMed:4030755). Belongs to the peptidase M27 family. A structure of a fragment of this protein in complex with the catalytic domain of C.botulinum neurotoxin type B (BoNT/B, botB) was reported; because of the lack of clear and continuous electron density for the VAMP2 peptide in the complex structure, the paper was retracted. One of its associated structures remains valid (PDB:1F82, light chain alone) (PubMed:10932255, PubMed:19578378).