Light Chain Diversity among the Botulinum Neurotoxins.

Light Chain Diversity among the Botulinum Neurotoxins.
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肉毒神经毒素之间的轻链多样性。

DOI:
10.3390/toxins10070268
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发表时间:
2018-07-02
期刊:
影响因子:
4.2
通讯作者:
Barbieri JT
Barbieri JT
中科院分区:
医学2区
文献类型:
--
作者:
Gardner AP;Barbieri JT

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肉毒杆菌神经毒素(BoNT)由几种梭菌产生。存在七种免疫学上独特的BoNT血清型(A-G)。疾病控制中心将BoNT归类为“A类”选择剂,是对人类最致命的蛋白质毒素。最近,BoNT样蛋白也已在几种非梭菌中鉴定。BoNT是由N-末端锌金属蛋白酶轻链(LC)和C-末端重链(HC)组成的双链蛋白,所述C-末端重链包括易位和受体结合结构域。这两条链由二硫键连接在一起。LC裂解可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体(SNARE)。SNARE的裂解抑制突触囊泡与细胞膜的融合以及随后的乙酰胆碱的释放,这导致弛缓性麻痹。LC控制BoNT作用的催化性质和持续时间。这篇综述讨论了LC催化,LC易位的机制,以及LC作用持续时间的基础。了解LC的这些特性可能会扩大BoNT作为人类疗法的应用。
Botulinum neurotoxins (BoNT) are produced by several species of clostridium. There are seven immunologically unique BoNT serotypes (A–G). The Centers for Disease Control classifies BoNTs as ‘Category A’ select agents and are the most lethal protein toxins for humans. Recently, BoNT-like proteins have also been identified in several non-clostridia. BoNTs are di-chain proteins comprised of an N-terminal zinc metalloprotease Light Chain (LC) and a C-terminal Heavy Chain (HC) which includes the translocation and receptor binding domains. The two chains are held together by a disulfide bond. The LC cleaves Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The cleavage of SNAREs inhibits the fusion of synaptic vesicles to the cell membrane and the subsequent release of acetylcholine, which results in flaccid paralysis. The LC controls the catalytic properties and the duration of BoNT action. This review discusses the mechanism for LC catalysis, LC translocation, and the basis for the duration of LC action. Understanding these properties of the LC may expand the applications of BoNT as human therapies.
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