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首页> 美国卫生研究院文献>The Journal of General Physiology >Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors
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Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors

机译：beta 2和beta 4的区域负责alpha 3 beta 2和alpha 3 beta 4神经元烟碱样受体的稳态剂量反应关系之间的差异

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摘要

We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC50 for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC50 of ACh dose-response relationship in the expected direction but does not completely convert the EC50 of the dose- response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors.
机译：我们构建了大鼠beta 2和beta 4神经元烟碱亚基的嵌合体，以定位有助于乙酰胆碱（ACh）剂量响应关系的alpha 3 beta 2和alpha 3 beta 4受体之间差异的区域。在非洲爪蟾卵母细胞中表达的alpha 3 beta 2受体对ACh的EC50大约比alpha 3 beta 4受体的EC50小20倍。 alpha 3 beta 2的表观Hill斜率（n（app））接近1，而alpha 3 beta 4受体的n（app）接近2。前120个残基内的取代将ACh的EC50从一种野生型值转换为另一种野生型值。仅将beta 2：2-104-120交换为beta 4的对应区域会将ACh剂量-反应关系的EC50沿预期方向移动，但并未将剂量-反应关系的EC50从一种野生型值完全转换为另一种野生型值。但是，β2：104-120区域的取代确实说明了α3β2受体对胱氨酸，四甲基铵和ACh的相对敏感性。 β4样（强）协作性的表达需要β4的广泛区域（β4：1-301）。相对较短的beta 2替代（beta 2：104-120）可以降低对beta 2类值的协作性。结果表明，β2的前120个残基和β4的相应区域内的氨基酸有助于形成激动剂结合位点，从而桥接神经元烟碱样受体中的α和β亚基。

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