Corringer P J, Bertrand S, Galzi J L, Devillers-Thiéry A, Changeux J P, Bertrand D
Neurobiologie Moléculaire, Unité de Recherche Associée au Centre National de la Recherche Scientifique D1284, Institut Pasteur, Paris, France.
Neuron. 1999 Apr;22(4):831-43. doi: 10.1016/s0896-6273(00)80741-2.
In the alpha7 nicotinic acetylcholine receptors, we analyze the contribution of mutations E237A and V251T, together with the proline insertion P236', in the conversion of the charge selectivity from cationic to anionic. We show that the triple mutant exhibits spontaneous openings displaying anionic selectivity. Furthermore, at position 251, hydrophilic or even negatively charged residues are compatible with an anionic channel. In contrast, the additional proline yields an anionic channel only when inserted between positions 234 and 237; insertion before 234 yields a cationic channel and after 238 alters the receptor surface expression. The coiled 234-238 loop thus directly contributes to the charge selectivity filter of the alpha7 channel.
在α7烟碱型乙酰胆碱受体中，我们分析了突变E237A和V251T以及脯氨酸插入P236'在电荷选择性从阳离子向阴离子转变过程中的作用。我们发现三重突变体呈现出自发开放并表现出阴离子选择性。此外，在第251位，亲水性甚至带负电荷的残基与阴离子通道兼容。相比之下，额外的脯氨酸只有插入到234位和237位之间时才会产生阴离子通道；在234位之前插入会产生阳离子通道，而在238位之后插入则会改变受体的表面表达。因此，234 - 238位的卷曲环直接对α7通道的电荷选择性过滤器起作用。
