Recombinant Clostridium botulinum Botulinum neurotoxin type E (botE), partial

Function

Responsible for host epithelial cell transcytosis, host nerve cell targeting and translocation of light chain (LC) into host cytosol (PubMed:17666397). Composed of 3 subdomains; the translocation domain (TD), and N-terminus and C-terminus of the receptor-binding domain (RBD). The RBD is responsible for the adherence of the toxin to the cell surface (PubMed:10413679). It probably simultaneously recognizes 2 coreceptors; polysialated gangliosides and either of the receptor proteins SV2A and SV2B in close proximity on host synaptic vesicles (PubMed:18815274, PubMed:19476346, PubMed:19650874). The N-terminus of the TD wraps an extended belt around the perimeter of the light chain (LC), protecting Zn(2+) in the active site (PubMed:19118561). The belt may also prevent premature LC dissociation from the translocation channel and protect toxin prior to translocation (PubMed:17907800). The TD inserts into synaptic vesicle membrane to allow translocation into the host cytosol (By similarity). Responsible for adherence of the toxin to the cell surface; HC alone prevents uptake of whole toxin by neural cells, and delays paralysis onset by 154% (PubMed:10413679). Significantly decreases uptake and toxicity of whole BoNT/E, but also interferes with uptake of BoNT/C; binds GT1b in vitro (PubMed:19650874). Binds to synaptic vesicle glycoproteins SV2A and SV2B which serve as coreceptors with gangliosides (PubMed:18815274, PubMed:19650874). Interaction with SV2 proteins requires SV2 glycosylation (PubMed:19476346). HC alone significantly decreases uptake and toxicity of whole BoNT/E (PubMed:19650874). HC is responsible for translocation of LC into the host cytosol; an intact disulfide bond between the 2 subunits is required for translocation, which is reduced upon contact with the host cytosol (PubMed:17666397)

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); cleavage occurs after bacterial export by host proteases (PubMed:19118561, PubMed:4030755, PubMed:6353669). The LC has the proteolytic/pharmacological activity, while the N- and C-terminal of the HC mediate channel formation and toxin binding, respectively. Oligomerizes in the presence of coreceptor ganglioside GT1b between pH 4.4 and 8.0; it might oligomerize on host cell surface (PubMed:22720883). Interacts with host synaptic vesicle glycoproteins SV2A and SV2B (PubMed:18815274, PubMed:19650874). HC interacts with a complex including at least host SV2 and synaptotagmin-1 (SYT1); copurification depends on glycosylation of SV2 (PubMed:19476346)

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