Fishing for holes in transporters: how protons breach the Na/K pump security gates.
Fishing for holes in transporters: how protons breach the Na/K pump security gates.
复制标题
寻找运输装置中的漏洞：质子如何突破 Na/K 泵的安全门。
DOI：
10.1085/jgp.201411189
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Hilgemann,DonaldW
中科院分区：
文献类型：
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作者：
Hilgemann,DonaldW
背景离子泵是修饰离子通道的想法对Peter Mitchell(1972)来说是显而易见的。Mitchell绘制了F-ATPase，好像F_o亚基构成了一个长的水溶液通道，通向ATP合成(或水解；见图1)的F_1位点。如果膜电位沿着这个狭窄的“通道”下降，那么驱动F-ATPase功能的膜电位和质子浓度的等效性就可以很好地解释了。彼得·L(1979年)对米切尔的思想进行了扩展和提炼：离子泵的两侧都有通道。在顺式一侧，接入通道在结合部位结束，该结合部位由大能量势垒底部的能量最小值表示。当离子被动占据结合部位时，能量的投资(光，在细菌视紫红质的情况下)然后改变能量分布，从而迫使离子通过反面的访问通道离开泵(见图1B)。这些想法随后被用于许多转运蛋白的研究(Apell，2004)，但他们发现哺乳动物钠转运蛋白的研究人员特别共鸣。
BackgroundThe idea that ion pumps are modified ion channels was obvious to Peter Mitchell (1972). Mitchell drew the F-ATPase as if the F o subunits constitute a long aqueous channel leading up to the F 1 sites of ATP synthesis (or hydrolysis; see Fig. 1 A). Equivalence of membrane potential and proton concentration in driving F-ATPase function could then be neatly explained if membrane potential would fall off along this narrow “access channel.” Mitchell’s thinking was extended and refined by Peter Läuger (1979): Access channels will exist on both sides of an ion pump. On the cis side, the access channel ends at a binding site, represented by an energy minimum at the base of a large energy barrier. When ions passively occupy the binding site, investment of energy (light, in the case of bacteriorhodopsin) then shifts the energy profiles so that the ions are forced to exit the pump through the access channel on the trans side (see Fig. 1 B). These ideas were subsequently put to use in the study of many transporters (Apell, 2004), but they found particular resonance with investigators of mammalian Na transporters.