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肉毒杆菌神经毒素重链和轻链在神经肌肉麻痹中的作用。

Role of the heavy and light chains of botulinum neurotoxin in neuromuscular paralysis.

作者信息

Bandyopadhyay S, Clark A W, DasGupta B R, Sathyamoorthy V

出版信息

J Biol Chem. 1987 Feb 25;262(6):2660-3.

PMID:3029090
Abstract

Botulinum neurotoxin (NT) is synthesized by Clostridium botulinum in any of seven antigenically distinct forms called types A-G. NT, when fully active, is a dichain protein, composed of two polypeptides, a heavy (H) and a light (L) chain (approximately 100,000 and approximately 50,000 Da, respectively) that are held together by noncovalent bonds and at least one disulfide bond. Two types of dichain NT, A and B, and their respective H and L chains were applied to nerve-muscle (NM) preparations (phrenic nerve-hemidiaphragm of the mouse), in order to develop a broader, comparative understanding of the neuroparalytic actions of NT types. It was found that the paralysis induced by dichain NT was delayed or antagonized if NM preparations were incubated with isolated and purified H chain prior to, or during, incubation with the parent, dichain NT. NM preparations preincubated with H chain and then washed free of unbound H chain became paralyzed after subsequent incubation with L chain. Paralysis did not occur if NM preparations were incubated first with L chain, washed, and then incubated with H chain. These observations suggest that the H chain binds with specific sites on the nerve terminal. This binding appears to permit the L chain, or some combination of the L and H chain, to bring about neuroparalysis through a mechanism very similar to that of the parent, dichain NT.

摘要

肉毒杆菌神经毒素(NT)由肉毒梭菌以七种抗原性不同的形式之一合成,分别称为A - G型。当NT完全具有活性时,它是一种双链蛋白,由两条多肽组成,一条重链(H)和一条轻链(L)(分别约为100,000道尔顿和约50,000道尔顿),它们通过非共价键和至少一个二硫键结合在一起。将两种双链NT,即A和B型,以及它们各自的H链和L链应用于神经肌肉(NM)制剂(小鼠膈神经 - 半膈肌),以便对不同类型NT的神经麻痹作用有更广泛的比较性理解。结果发现,如果在与亲本双链NT孵育之前或期间,将NM制剂与分离纯化的H链一起孵育,双链NT诱导的麻痹会延迟或受到拮抗。先用H链预孵育NM制剂,然后洗去未结合的H链,随后与L链孵育后,NM制剂会发生麻痹。如果NM制剂先与L链孵育,洗涤后再与H链孵育,则不会发生麻痹。这些观察结果表明,H链与神经末梢上的特定位点结合。这种结合似乎允许L链或L链与H链的某种组合,通过一种与亲本双链NT非常相似的机制导致神经麻痹。

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