肉毒杆菌毒素 B 的毒性
中文名称
通路描述
肉毒杆菌毒素 B (botB，也称为 BoNT/B)，是一种二硫键连接的轻链 (LC) - 重链 (HC) 异二聚体，通常以与含非毒性非血凝素蛋白 (NTNHA，由 C. botulinum ntnha 基因编码) 复合物及多个 3 个血凝素蛋白 (HA，由 C. botulinum ha17, ha34 和 ha70 基因编码) 复合物形式进入肠道 (Amatsu 等人 2013)。该复合物保护毒素免受肠道内降解，介导其与肠上皮细胞的结合及跨转运以进入循环 (Fujinaga 等人 2013)。循环毒素分子与突触囊泡蛋白 2 (SV2) 结合，该蛋白在突触囊泡释放时暴露于突触囊泡膜胞质面 (Dong 等人 2003; Yowler & Schengrund 2004)。囊泡回收将毒素带入神经元，此时囊泡酸化 (Sudhoff 2004)。pH 降低诱导毒素发生构象变化：其 HC 在囊泡膜中形成通道，使 LC 被挤出至神经元胞质 (Montal 2010)。随后，LC 催化切割突触囊泡膜蛋白 2 (VAMP2) 的胞质面 (Foran 等人 1994; Schiavo 等人 1992)，从而抑制突触囊泡与细胞膜的融合及胞吐。
英文描述
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.
所含基因
4 个基因