Asymmetric Operations Department, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA.
Curr Top Microbiol Immunol. 2013;364:115-37. doi: 10.1007/978-3-642-33570-9_6.
Clostridium botulinum neurotoxin (BoNT) is a multidomain protein in which the individual modules work in synchronized cooperative action in order to enter into neurons and inhibit synaptic transmission. The di-chain protein is made up of the ~50 kD light chain and the ~100 kD heavy chain. The HC can be further subdivided into the N-terminal translocation domain (H(N)) and the C-terminal Receptor Binding Domain (H(C)). BoNT entry into neurons requires the toxin to utilize the host cell's endocytosis pathway where it exploits the acidic environment of the endosome. Within the endosome the H(C) triggers the H(N) to change conformation from a soluble protein to a membrane inserted protein-conducting channel in precise timing with LC refolding. The LC must partially unfold to a translocation competent conformation in order to be translocated by the H(N) channel in an N to C terminal direction. Upon completion of translocation, the LC is released from the HC and allowed to interact with its substrate SNARE protein. This article discusses the individual functions of each module as well as the mechanisms by which each domain serves as a chaperone for the others, working in concert to achieve productive intoxication.
肉毒梭菌神经毒素（BoNT）是一种多结构域蛋白，其中各个模块以同步协同的方式协同工作，以便进入神经元并抑制突触传递。双链蛋白由50 kD 轻链和100 kD 重链组成。HC 可进一步细分为 N 端易位结构域（H(N)）和 C 端受体结合结构域（H(C)）。BoNT 进入神经元需要毒素利用宿主细胞的内吞作用途径，在该途径中，毒素利用内体的酸性环境。在内体中，H(C)触发 H(N)改变构象，从可溶性蛋白转变为膜插入蛋白导通道，与 LC 重折叠精确同步。LC 必须部分展开到易位能力构象，以便由 H(N)通道沿 N 到 C 末端方向易位。易位完成后，LC 从 HC 释放，并允许与其底物 SNARE 蛋白相互作用。本文讨论了每个模块的单独功能以及每个结构域如何作为其他结构域的伴侣蛋白发挥作用，协同工作以实现有效的中毒。
