Edmonds D T
Clarendon Laboratory, Oxford, UK.
Eur Biophys J. 1989;17(3):113-9. doi: 10.1007/BF00254764.
Electrically charged residues in a membrane channel protein will certainly have a direct effect upon its gating and selectivity if they are near the channel pore. It is customary to regard the charged state of such residues as a fixed feature of the channel. In this paper it is argued that far from being fixed, the charged state of ionizable residues near the pore will very probably change rapidly in response to the channel opening and to ions passing through it. Calculations are presented using simple models which demonstrate that changes in the dielectric environment and changes in the distances to other charged groups resulting from channel opening can shift the effective pK values of the sites by 3 or 4 units leading to switching of its charged state. Examples are given of how this time dependent charge state of ionizable residues may play an important role in the functioning of channels. Also, by considering the influence of the electric field due to the mobile ion upon the charge state of a residue in the channel wall, it is shown that a channel lined with acid residues may very effectively block the passage of cations while allowing the passage of anions.
如果膜通道蛋白中的带电残基靠近通道孔，那么它们肯定会对通道的门控和选择性产生直接影响。通常认为这些残基的带电状态是通道的一个固定特征。本文认为，靠近孔的可电离残基的带电状态远非固定不变，很可能会随着通道打开以及离子通过通道而迅速变化。使用简单模型进行的计算表明，通道打开导致的介电环境变化以及与其他带电基团距离的变化，可使位点的有效pK值移动3或4个单位，从而导致其带电状态的转变。文中给出了可电离残基这种随时间变化的带电状态如何在通道功能中发挥重要作用的例子。此外，通过考虑移动离子产生的电场对通道壁中残基带电状态的影响，结果表明，内衬酸性残基的通道可能非常有效地阻止阳离子通过，同时允许阴离子通过。
