Unique mechanisms of gastric proton pump revealed by

随着食物的摄入，我们胃的pH值会达到1左右。这种高酸性环境是由胃质子泵、H+、K+- atp酶产生的，因此是酸相关疾病的重要药物靶点。除了作为药物靶点的重要意义外，胃H+，K+- atp酶还面临着一项非凡的任务，即在从细胞pH 7到胃pH 1的百万倍梯度下泵送质子。维持六个数量级的有效浓度梯度是自然界中任何其他膜泵难以满足的。质子泵是如何产生百万倍的氢离子梯度的？一个关键的要求是传输化学计量。通过改进碳夹芯法制备的二维晶体的电子晶体学，我们确定了H+，K+- atp酶的单一Rb+结合结构，我们展示了1H+/1Rb+/1ATP传输模式的独特结构证据，这是在膜上产生强质子梯度的先决条件。

In response to food intake, pH of our stomach reaches around 1. This highly acidic environment is generated by Gastric proton pump, H+,K+-ATPase, therefore a prominent drug target for the acid-related diseases. Besides its significant interest as a drug target, gastric H+,K+-ATPase faces a remarkable task of pumping protons against a million-fold gradient ranging from pH 7 in the cell to 1 in the stomach. Maintaining a potent concentration gradient of six orders of magnitude is hardly met by any other membrane pump in nature. How does the proton pump generate a million-fold H+ gradient?A key requirement is the transport stoichiometry. By determining a single Rb+-bound structure of H+,K+-ATPase by electron crystallography of 2D crystals prepared by improved carbon sandwich method, we showed the unique structural evidence of 1H+/1Rb+/1ATP transport mode, which is prerequisite for the generation of the potent proton gradient across the membrane.