Adcock C, Smith G R, Sansom M S
Laboratory of Molecular Biophysics, University of Oxford, England.
Biophys J. 1998 Sep;75(3):1211-22. doi: 10.1016/S0006-3495(98)74040-8.
The nicotinic acetylcholine receptor (nAChR) is a cation-selective ion channel that opens in response to acetylcholine binding. The related glycine receptor (GlyR) is anion selective. The pore-lining domain of each protein may be modeled as a bundle of five parallel M2 helices. Models of the pore-lining domains of homopentameric nAChR and GlyR have been used in continuum electrostatics calculations to probe the origins of ion selectivity. Calculated pKA values suggest that "rings" of acidic or basic side chains at the mouths of the nAChR or GlyR M2 helix bundles, respectively, may not be fully ionized. In particular, for the nAChR the ring of glutamate side chains at the extracellular mouth of the pore is predicted to be largely protonated at neutral pH, whereas those glutamate side chains in the intracellular and intermediate rings (at the opposite mouth of the pore) are predicted to be fully ionized. Inclusion of the other domains of each protein represented as an irregular cylindrical tube in which the M2 bundles are embedded suggests that both the M2 helices and the extramembrane domains play significant roles in determining ion selectivity.
烟碱型乙酰胆碱受体（nAChR）是一种阳离子选择性离子通道，它在乙酰胆碱结合后打开。相关的甘氨酸受体（GlyR）是阴离子选择性的。每种蛋白质的孔衬里结构域可以被模拟为一束五个平行的M2螺旋。同五聚体nAChR和GlyR的孔衬里结构域模型已用于连续介质静电计算，以探究离子选择性的起源。计算得到的pKA值表明，nAChR或GlyR的M2螺旋束口处的酸性或碱性侧链“环”可能未完全电离。特别是，对于nAChR，孔的细胞外口处的谷氨酸侧链环预计在中性pH下大部分被质子化，而细胞内和中间环（在孔的相对口处）的那些谷氨酸侧链预计会完全电离。将每种蛋白质的其他结构域表示为嵌入M2束的不规则圆柱形管，这表明M2螺旋和膜外结构域在决定离子选择性方面都起着重要作用。
