What ATP binding does to the Ca2+ pump and how nonproductive phosphoryl transfer is prevented in the absence of Ca2+
What ATP binding does to the Ca2+ pump and how nonproductive phosphoryl transfer is prevented in the absence of Ca2+
复制标题
DOI：
10.1073/pnas.2006027117
复制
发表时间：
2020-08-04
影响因子：
11.1
通讯作者：
Toyoshima, Chikashi
中科院分区：
文献类型：
--
作者：
Kabashima, Yoshiki;Ogawa, Haruo;Toyoshima, Chikashi
在生理条件下，大多数Ca 2 +-ATP酶（SERCA）分子在结合转运的Ca 2+之前结合ATP。即使在没有Ca 2+的情况下，SERCA也对ATP具有高亲和力，并且ATP在低于7的pH值下加速Ca 2+结合，其中SERCA处于具有低亲和力Ca 2+结合位点的E2状态。在这里，我们描述了SERCA 2a的晶体结构，在心肌中占主导地位的异构体，在E2中心点ATP状态在3.0埃的分辨率。在晶体结构中，胞质结构域的排列与典型的E2中的排列明显不同。A-结构域现在占据E1位置，N-结构域占据与E1中心点ATP中心点2Ca（2+）状态中相对于P-结构域的位置完全相同的位置。因此，ATP被正确地递送到磷酸化位点。然而，如果没有两个跨膜Ca 2+结合位点的填充，磷酰基转移就不会发生。目前的晶体结构解释了ATP结合本身对SERCA的作用，以及如何在E2中阻止非生产性磷酸化。
Under physiological conditions, most Ca2+-ATPase (SERCA) molecules bind ATP before binding the Ca2+ transported. SERCA has a high affinity for ATP even in the absence of Ca2+, and ATP accelerates Ca2+ binding at pH values lower than 7, where SERCA is in the E2 state with low-affinity Ca2+-binding sites. Here we describe the crystal structure of SERCA2a, the isoform predominant in cardiac muscle, in the E2 center dot ATP state at 3.0-angstrom resolution. In the crystal structure, the arrangement of the cytoplasmic domains is distinctly different from that in canonical E2. The A-domain now takes an E1 position, and the N-domain occupies exactly the same position as that in the E1 center dot ATP center dot 2Ca(2+) state relative to the P-domain. As a result, ATP is properly delivered to the phosphorylation site. Yet phosphoryl transfer never takes place without the filling of the two transmembrane Ca2+-binding sites. The present crystal structure explains what ATP binding itself does to SERCA and how nonproductive phosphorylation is prevented in E2.