Botulinum neurotoxin E heavy chain: 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:19650874, PubMed:19476346). 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).

Belongs to the peptidase M27 family.

1251 amino acids

MPKINSFNYNDPVNDRTILYIKPGGCQEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTSLKNGDSSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTPDNQFHIGDASAVEIKFSNGSQDILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHRFGSIAIVTFSPEYSFRFNDNCMNEFIQDPALTLMHELIHSLHGLYGAKGITTKYTITQKQNPLITNIRGTNIEEFLTFGGTDLNIITSAQSNDIYTNLLADYKKIASKLSKVQVSNPLLNPYKDVFEAKYGLDKDASGIYSVNINKFNDIFKKLYSFTEFDLRTKFQVKCRQTYIGQYKYFKLSNLLNDSIYNISEGYNINNLKVNFRGQNANLNPRIITPITGRGLVKKIIRFCKNIVSVKGIRKSICIEINNGELFFVASENSYNDDNINTPKEIDDTVTSNNNYENDLDQVILNFNSESAPGLSDEKLNLTIQNDAYIPKYDSNGTSDIEQHDVNELNVFFYLDAQKVPEGENNVNLTSSIDTALLEQPKIYTFFSSEFINNVNKPVQAALFVSWIQQVLVDFTTEANQKSTVDKIADISIVVPYIGLALNIGNEAQKGNFKDALELLGAGILLEFEPELLIPTILVFTIKSFLGSSDNKNKVIKAINNALKERDEKWKEVYSFIVSNWMTKINTQFNKRKEQMYQALQNQVNAIKTIIESKYNSYTLEEKNELTNKYDIKQIENELNQKVSIAMNNIDRFLTESSISYLMKIINEVKINKLREYDENVKTYLLNYIIQHGSILGESQQELNSMVTDTLNNSIPFKLSSYTDDKILISYFNKFFKRIKSSSVLNMRYKNDKYVDTSGYDSNININGDVYKYPTNKNQFGIYNDKLSEVNISQNDYIIYDNKYKNFSISFWVRIPNYDNKIVNVNNEYTIINCMRDNNSGWKVSLNHNEIIWTFEDNRGINQKLAFNYGNANGISDYINKWIFVTITNDRLGDSKLYINGNLIDQKSILNLGNIHVSDNILFKIVNCSYTRYIGIRYFNIFDKELDETEIQTLYSNEPNTNILKDFWGNYLLYDKEYYLLNVLKPNNFIDRRKDSTLSINNIRSTILLANRLYSGIKVKIQRVNNSSTNDNLVRKNDQVYINFVASKTHLFPLYADTATTNKEKTIKISSSGNRFNQVVVMNSVGNCTMNFKNNNGNNIGLLGFKADTVVASTWYYTHMRDHTNSNGCFWNFISEEHGWQEK

143.8 kDa

(Note: Representative image - actual molecular weight may vary depending on tag type and expression method)

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