首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Alpha-Bungarotoxin binding to human muscle acetylcholine receptor: measurement of affinity, delineation of AChR subunit residues crucial to binding, and protection of AChR function by synthetic peptides.
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Alpha-Bungarotoxin binding to human muscle acetylcholine receptor: measurement of affinity, delineation of AChR subunit residues crucial to binding, and protection of AChR function by synthetic peptides.

机译:与人肌肉乙酰胆碱受体结合的α-真菌毒素:亲和力的测量,对结合至关重要的AChR亚基残基的描绘以及合成肽对AChR功能的保护。

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摘要

Alpha-Bungarotoxin (alpha-BuTx) binds with high affinity to the nicotinic acetylcholine receptor (AChR) of most species, mainly to sequences around the two cysteines at positions 192 and 193 of the alpha-subunit, but other sequences of the alpha-subunit and of the adjacent gamma- or epsilon- and delta-subunits are also important in the native molecule. Alpha-BuTx binds strongly to human AChR but the short alpha neurotoxins, for instance Erabutoxin B, are relatively ineffective at the human neuromuscular junction. In this article we compare the affinity of 125I-alpha-BuTx for Torpedo and human muscle AChR and the ability of neurotoxins to inhibit this binding. We examine the contribution to alpha-BuTx binding of the three amino acids that differ between human and Torpedo AChR alpha-185-196. In addition, we show that an alpha-185-199, peptide that binds strongly to 125I-alpha-BuTx and can inhibit its binding in solution, is also capable of protecting the AChR on a cell line or at the neuromuscular junction. Such peptides might be useful in the treatment of acute envenoming or the autoantibody-mediated block of AChR function that can occur in human disorders.
机译:α-真菌毒素(α-BuTx)与大多数物种的烟碱乙酰胆碱受体(AChR)具有高亲和力,主要与α亚基192和193位两个半胱氨酸周围的序列结合,但α亚基的其他序列在天然分子中,相邻的γ-或ε-亚基和δ-亚基中的“α”也很重要。 Alpha-BuTx与人AChR牢固结合,但是短的α神经毒素,例如伊曲丁毒素B,在人的神经肌肉接头处相对无效。在本文中,我们比较了125I-alpha-BuTx对鱼雷和人肌肉AChR的亲和力以及神经毒素抑制这种结合的能力。我们检查了人类和鱼雷AChR alpha-185-196之间不同的三个氨基酸对alpha-BuTx结合的贡献。此外,我们显示了与125I-α-BuTx牢固结合并可以抑制其在溶液中的结合的α-185-199肽也能够保护细胞系或神经肌肉接头处的AChR。此类肽可用于治疗人类疾病中可能发生的急性毒化或自身抗体介导的AChR功能阻滞。

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