Toxicity of botulinum toxin type B (botB)

Botulinum toxin type B (botB, also known as BoNT/B), a disulfide-bonded heavy chain (HC) - light chain (LC) heterodimer, enters the gut typically as a result of consuming contaminated food (Hatheway 1995), as a complex with nontoxic nonhemagglutinin protein (NTNHA, encoded by the C. botulinum ntnha gene) and multiple copies of three hemagglutinin proteins (HA, encoded by the C. botulinum ha17, ha34, and ha70 genes) (Amatsu et al. 2013). The complex protects the toxin from degradation in the gut and mediates its association with the gut epithelium and transcytosis to enter the circulation (Fujinaga et al. 2013). Circulating toxin molecules associate with gangliosides and synaptotagmin (SYT) proteins exposed by exocytosis at a synapse of a target neuron (Dong et al. 2003; Yowler & Schengrund 2004). Vesicle recycling brings the toxin into the neuron where the vesicle is acidified (Sudhoff 2004). The lowered pH induces a conformational change in the toxin: its HC forms a passage in the vesicle membrane through which its LC is extruded into the neuronal cytosol. Tthe HC - LC disulfide bond is reduced (Montal 2010). The LC then catalyzes the cleavage of vesicle-associated membrane protein 2 (VAMP2) on the cytosolic face of synaptic vesicle membranes (Foran et al. 1994; Schiavo et al. 1992), thereby inhibiting synaptic vesicle fusion with the plasma membrane and exocytosis.

肉毒毒素B型（botB，亦称BoNT/B），一种由二硫键连接的重链（HC）-轻链（LC）异二聚体，通常因食用受污染的食物而进入肠道（Hatheway 1995），并与非毒性非血凝素蛋白（NTNHA，由肉毒杆菌的ntnha基因编码）以及三份拷贝的三种血凝素蛋白（HA，由肉毒杆菌的ha17、ha34和ha70基因编码）形成复合物（Amatsu等，2013年）。该复合物保护毒素免受肠道降解，并介导其与肠道上皮细胞的结合及跨细胞转运至血液循环中（Fujinaga等，2013年）。循环中的毒素分子与由目标神经元突触的胞吐作用暴露的神经节苷脂和突触素（SYT）蛋白结合（Dong等，2003年；Yowler & Schengrund，2004年）。囊泡的回收将毒素带入神经元内部，其中囊泡被酸性化（Sudhoff，2004年）。降低的pH值诱导毒素发生构象变化：其HC在囊泡膜中形成一个通道，通过该通道其LC被排出至神经元细胞质中。HC-LC的二硫键被还原（Montal，2010年）。随后，LC催化位于突触囊泡膜细胞质面的囊泡相关膜蛋白2（VAMP2）的裂解（Foran等，1994年；Schiavo等，1992年），从而抑制突触囊泡与质膜的融合及胞吐作用。