肉毒毒素 E 的毒性
中文名称
通路描述
肉毒毒素 E (botE，也称为 BoNT/E) 是一种二硫键连接的轻链 (LC) - 重链 (HC) 异二聚体（'双链'），通常以与无毒非血凝素蛋白 (NTNHA，由 C. botulinum ntnha 基因编码) 复合物形式进入肠道 (Benefield et al. 2013)。该复合物保护毒素免受肠道降解，介导其与肠道上皮结合及跨转运以进入循环 (Fujinaga et al. 2013)。循环毒素分子与靶神经元突触外泌时暴露的糖脂和突触囊泡蛋白 2 (SV2) 结合 (Dong et al. 2008; Yowler & Schengrund 2004)。囊泡回收将毒素带入神经元，囊泡被酸化 (Sudhoff 2004)。较低的 pH 诱导毒素发生构象变化：其 HC 形成囊泡膜通道，其 LC 被 HC - LC 二硫键还原后挤出至神经元胞质并释放 (Montal 2010)。LC 随后催化切割神经元细胞膜胞质面上的突触囊泡相关蛋白 25 (SNAP25) (Binz et al. 1994; Schiavo et al. 1993)，从而抑制突触囊泡与细胞膜的融合和外泌。
英文描述
Toxicity of botulinum toxin type E (botE) Botulinum toxin type E (botE, also known as BoNT/E), a disulfide-bonded heavy chain (HC) - light chain (LC) heterodimer (âdichainâ), 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) (Benefield 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 synaptic vesicle protein 2 (SV2) exposed by exocytosis at a synapse of a target neuron (Dong et al. 2008; 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 and released by reduction of the HC - LC disulfide bond (Montal 2010). The LC then catalyzes the cleavage of synaptosome-associated protein 25 (SNAP25) on the cytosolic face of the neuronal plasma membrane (Binz et al. 1994; Schiavo et al. 1993), thereby inhibiting synaptic vesicle fusion with the plasma membrane and exocytosis.
所含基因
4 个基因