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首页> 外文期刊>Journal of Molecular Biology >Activation of the nicotinic acetylcholine receptor involves a switch in conformation of the alpha subunits.
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Activation of the nicotinic acetylcholine receptor involves a switch in conformation of the alpha subunits.

机译：烟碱乙酰胆碱受体的活化涉及α亚基构象的转换。

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摘要

The nicotinic acetylcholine (ACh) receptor belongs to a superfamily of synaptic ion channels that open in response to the binding of chemical transmitters. Their mechanism of activation is not known in detail, but a time-resolved electron microscopic study of the muscle-type ACh receptor had suggested that a local disturbance in the ligand-binding region and consequent rotations in the ligand-binding alpha subunits, connecting to the transmembrane portion, are involved. A more precise interpretation of this structural change is given here, based on comparison of the extracellular domain of the ACh receptor with an ACh-binding protein (AChBP) to which a putative agonist is bound. We find that, to a good approximation, there are two alternative extended conformations of the ACh receptor subunits, one characteristic of either alpha subunit before activation, and the other characteristic of all three non-alpha subunits and the protomer of AChBP. Substitution in the three-dimensional maps of alpha by non-alpha subunits mimics the changes seen on activation, suggesting that the structures of the alpha subunits are modified initially by their interactions with neighbouring subunits and switch to the non-alpha form when ACh binds. This structural change, which entails 15-16 degrees rotations of the inner pore-facing parts of the alpha subunits, most likely acts as the trigger that opens the gate in the membrane-spanning pore.
机译：烟碱型乙酰胆碱（ACh）受体属于突触离子通道的超家族，其响应化学递质的结合而打开。他们的激活机制尚不清楚，但是对肌肉型ACh受体的时间分辨电子显微镜研究表明，配体结合区域发生局部干扰，配体结合α亚基随之旋转，与涉及跨膜部分。根据比较ACh受体的胞外域与推定激动剂所结合的ACh结合蛋白（AChBP）的情况，在此给出了对该结构变化的更精确解释。我们发现，以一个很好的近似，ACh受体亚基有两个替代的扩展构象，一个是激活前一个α亚基的特征，另一个是所有三个非α亚基和AChBP的前体的特征。非α亚基在α三维图中的替换模拟了激活时看到的变化，这表明α亚基的结构最初是通过与相邻亚基的相互作用而被修饰的，并在ACh结合后转变为非α形式。这种结构变化需要α亚基的面向内孔的部分旋转15-16度，最有可能充当触发因素，在跨膜孔中打开闸门。

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