Recombinant Clostridium botulinum Botulinum neurotoxin type B (botB), partial

Function

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:17167418, PubMed:17167421, PubMed:17185412, PubMed:23807078, PubMed:8144634). 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:17167418, PubMed:21925111). 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:17167418, PubMed:17167421, PubMed:23807078). Has higher affinity for SYT2 than SYT1 (PubMed:17167421, PubMed:17185412). Significantly decreases uptake and toxicity of whole BoNT/B and BoNT/G (PubMed:19650874)

Subcellular Location

Secreted; Host synapse, host presynaptic cell membrane; Host cytoplasmic vesicle, host secretory vesicle, host synaptic vesicle membrane (Multi-pass membrane protein)

Subunit

Heterodimer; disulfide-linked heterodimer of a light chain (LC) and a heavy chain (HC) (PubMed:1331807, PubMed:3139097). 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:14504267, PubMed:19650874, PubMed:8144634). Interacts with host receptor synaptotagmin-2 (SYT2) (PubMed:14504267, PubMed:15123599, PubMed:17167418, PubMed:17167421, PubMed:19650874, 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)

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• Szabo E.A. et al. PubMed: CI-590HSGJ8B7EB (APR-)
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