Function
Botulinum neurotoxin B heavy chain: 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).
Sequence
MPVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCKSVKAPGICIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDKIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNSEILNNIILNLRYKDNNLIDLSGYGAKVEVYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIHNEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTITNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKYNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYFKKEEEKLFLAPISDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESGIVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTE