How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump
How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump
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DOI：
10.1073/pnas.0709978104
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发表时间：
2007-12-11
影响因子：
11.1
通讯作者：
Ogawa, Haruo
中科院分区：
文献类型：
--
作者：
Toyoshima, Chikashi;Norimatsu, Yoshiyuki;Ogawa, Haruo
骨骼肌肌浆网的 Ca2+-ATP 酶是 P 型或 E1/E2 型离子转运 ATP 酶中研究最多的成员。它以七种不同的状态结晶，几乎涵盖了整个反应周期。在这里，我们描述了在没有 Ca2+ 的情况下与磷酸类似物 BeF3- 和 AIF(4)(-) 复合的 ATP 酶的结构，它们分别对应于 E2P 基态和类似于 P 过渡态的 E2。管腔门用 BeF3- 打开，用 AIF4- 关闭。这些和类似于P中心点ADP模拟晶体结构的El表明，细胞质A域的两步旋转通过MI-M4跨膜螺旋的运动打开和关闭管腔门。有几种与旋转相关的构象开关，其中 M2 细胞质部分的构象开关至关重要。在旋转的第二步中，一个水分子的定位将天冬氨酰磷酸的水解与门的关闭耦合起来。
Ca2+-ATPase of skeletal muscle sarcoplasmic reticulum is the best-studied member of the P-type or E1/E2 type ion transporting ATPases. It has been crystallized in seven different states that cover nearly the entire reaction cycle. Here we describe the structure of this ATPase complexed with phosphate analogs BeF3- and AIF(4)(-) in the absence of Ca2+, which correspond to the E2P ground state and E2 similar to P transition state, respectively. The luminal gate is open with BeF3- and closed with AIF4-. These and the El similar to P center dot ADP analog crystal structures show that a two-step rotation of the cytoplasmic A-domain opens and closes the luminal gate through the movements of the MI-M4 transmembrane helices. There are several conformational switches coupled to the rotation, and the one in the cytoplasmic part of M2 has critical importance. In the second step of rotation, positioning of one water molecule couples the hydrolysis of aspartyl phosphate to closing of the gate.