The Mechanism of Ca 2 1 Transport by Sarco ( Endo ) plasmic Reticulum Ca 2 1-ATPases *
The Mechanism of Ca 2 1 Transport by Sarco ( Endo ) plasmic Reticulum Ca 2 1-ATPases *
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发表时间：
1997
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通讯作者：
D. Maclennan;W. Rice;N. Green
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作者：
D. Maclennan;W. Rice;N. Green
功能钙泵与钙释放通道共同构成了肌肉和非肌肉细胞中普遍存在的钙调节系统。肌浆网Ca-ATP酶（SERCA）和质膜Ca-ATP酶对从细胞质中去除Ca具有最高的亲和力，并且一起设定静息细胞质Ca浓度。三个差异表达的基因编码SERCA蛋白（1）。SERCA 1a和-1b在快速收缩骨骼肌中表达，但布罗迪病中SERCA 1功能的丧失足以补偿以维持生命（2）。SERCA 2a是心脏/慢收缩同种型，而SERCA 2b具有C末端延伸，在平滑肌和非肌肉组织中表达。几乎可以肯定，它是一种重要的基因。SERCA 3在有限的非肌肉组织中表达，包括内皮细胞、上皮细胞和淋巴细胞以及血小板，并且其敲除不是致命的（3）。SERCA酶是典型的P型ATP酶，其形成磷蛋白中间体并在ATP水解过程中经历构象变化（4，5）。一些构象状态可以通过调节反应条件或通过诱变来稳定，并表征为整个反应循环中的中间体（图1A）。磷酸化中间体E1 P（Ca）2可以磷酸化ADP，而E2 P只能与水反应。E1 P的形成需要两个高亲和力的Ca结合位点被占据。然后，该酶被ATP磷酸化，同时，两个Ca离子被封闭，不能再与细胞质Ca交换。向E2 P的限速转变伴随着Ca 21的损失
Function Ca pumps, together with Ca release channels, form ubiquitous Ca regulatory systems in muscle and non-muscle cells. The sarco(endo)plasmic reticulum Ca-ATPases (SERCA) and the plasma membrane Ca-ATPases have the highest affinity for Ca removal from the cytoplasm and, together, set resting cytoplasmic Ca concentrations. Three differentially expressed genes encode SERCA proteins (1). SERCA1a and -1b are expressed in fast-twitch skeletal muscle, but loss of SERCA1 function in Brody disease is sufficiently compensated to preserve life (2). SERCA2a is the cardiac/slow-twitch isoform, whereas SERCA2b, with a C-terminal extension, is expressed in smooth muscle and non-muscle tissues. It is almost certainly an essential gene. SERCA3 is expressed in a limited set of non-muscle tissues, including endothelial, epithelial, and lymphocytic cells and platelets, and its knockout is not lethal (3). SERCA enzymes are typical of the class of P-type ATPases, which form a phosphoprotein intermediate and undergo conformational changes during the course of ATP hydrolysis (4, 5). Some of the conformational states can be stabilized, either by adjustment of reaction conditions or through mutagenesis, and characterized as intermediates in the overall reaction cycle (Fig. 1A). The phosphorylated intermediate, E1P(Ca)2, can phosphorylate ADP, whereas E2P can only react with water. The formation of E1P requires that two high affinity Ca binding sites be occupied. The enzyme is then phosphorylated by ATP and, concomitantly, the two Ca ions are occluded and can no longer exchange with cytoplasmic Ca. The rate-limiting transition to E2P is accompanied by loss of Ca 21