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首页> 外文期刊>The Biochemical Journal >Identification of regions involved in the binding of alpha-bungarotoxin to the human alpha 7 neuronal nicotinic acetylcholine receptor using synthetic peptides
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Identification of regions involved in the binding of alpha-bungarotoxin to the human alpha 7 neuronal nicotinic acetylcholine receptor using synthetic peptides

机译：使用合成肽鉴定涉及α-邦格鲁毒素与人α7神经元烟碱型乙酰胆碱受体结合的区域

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The neuronal alpha7 nicotinic acetylcholine receptor (AM) binds the neurotoxin alpha-bungarotoxin (alpha-Bgt). Fine mapping of the alpha-Bgt-binding site on the human alpha7 AChR was performed using synthetic peptides covering the entire extracellular domain of the human alpha7 subunit (residues 1-206). Screening of these peptides for I-125-alpha-Bgt binding resulted in the identification of at least two toxin-binding sites, one at residues 186-197, which exhibited the best I-125-alpha-Bgt binding, and one at residues 159-165, with weak toxin-binding capacity; these correspond, respectively, to loops C and IV of the agonist-binding site. Toxin binding to the alpha7(186-197) peptide was almost completely inhibited by unlabelled alpha-Bgt or d-tubocurarine. Alanine substitutions within the sequence 186-198 revealed a predominant contribution of aromatic and negatively charged residues to the binding site. This sequence is homologous to the alpha-Bgt binding site of the alpha1 subunit (residues 188-200 in Torpedo AM). In competition experiments, the soluble peptides alpha7(186-197) and Torpedo alpha1(184-200) inhibited the binding of I-125-alpha-Bgt to the immobilized alpha7(186-197) peptide, to native Torpedo AChR, and to the extracellular domain of the human alpha1 subunit. These results suggest that the toxin-binding sites of the neuronal alpha7 and muscle-type AChRs bind to identical or overlapping sites on the alpha-Bgt molecule. In support of this, when synthetic alpha-Bgt peptides were tested for binding to the recombinant extracellular domains of the human alpha7 and alpha1 subunits, and to native Torpedo and alpha7 AChR, the results indicated that alpha-Bgt interacts with both neuronal and muscle-type AChRs through its central loop II and C-terminal tail. [References: 51]
机译：神经元的α7烟碱乙酰胆碱受体（AM）与神经毒素α-真菌毒素（α-Bgt）结合。使用覆盖人α7亚基的整个胞外结构域（残基1-206）的合成肽，对人α7AChR上的α-Bgt结合位点进行精细定位。对这些肽进行I-125-α-Bgt结合的筛选导致鉴定出至少两个毒素结合位点，一个在残基186-197处，表现出最佳的I-125-α-Bgt结合，一个在残基处159-165，毒素结合能力弱;这些分别对应于激动剂结合位点的环C和IV。毒素与alpha7（186-197）肽的结合几乎完全被未标记的alpha-Bgt或d-微管尿素抑制。序列186-198内的丙氨酸取代显示出芳香族和带负电荷的残基对结合位点的主要贡献。该序列与α1亚基的α-Bgt结合位点（Torpedo AM中的残基188-200）同源。在竞争实验中，可溶性肽α7（186-197）和鱼雷α1（184-200）抑制了I-125-α-Bgt与固定的α7（186-197）肽，天然鱼雷AChR和人alpha1亚基的胞外域。这些结果表明，神经元α7和肌肉型AChR的毒素结合位点与α-Bgt分子上的相同或重叠位点结合。为了证明这一点，当测试合成的α-Bgt肽与人α7和α1亚基的重组胞外域以及天然鱼雷和α7AChR的结合时，结果表明α-Bgt与神经元和肌肉相互作用。通过其中央环II和C末端尾巴来控制AChR型。 [参考：51]

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