Carafoli E
Laboratory of Biochemistry III, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
Basic Res Cardiol. 1997;92 Suppl 1:59-61. doi: 10.1007/BF00794069.
The plasma membrane Ca-pump (134 kDa) is stimulated by calmodulin and by other treatments (exposure to acidic phospholipids, treatments with proteases, phosphorylation by protein kinases A or C, self-association to form oligomers). It is the product of four genes (in humans), but additional isoforms originate through alternative mRNA spicing. Most of the pump mass protrudes into the cytoplasm with three main units. The calmodulin binding domain is located in the C-terminal protruding unit. The domain is a positively charged segment of about 25 residues. The calcium-activated protease calpain activates the pump by removing its calmodulin binding domain and the portion C-terminal to it. The-resulting 124 KDa fragment has been used to test the suggestion of an autoinhibitory function of the calmodulin binding domain. The latter interacts with two domains of the pump, one located close to the active site in the mid-cytoplasmic protruding unit, the other in the first (N-terminal) protruding unit. The isoforms of the pump show variations in the regulatory domains, e.g., alternative mRNA splicing can eliminate the domain phosphorylated by protein kinase A, or alter the sensitivity of the pump to calmodulin. This occurs by inserting sequences rich in His between calmodulin binding subdomains A and B. The inserted domain(s) confer pH sensitivity to the binding of calmodulin. Calcium binding sites have been found in acidic regions preceding and following the calmodulin binding domain.
质膜钙泵（134 kDa）受钙调蛋白及其他处理（暴露于酸性磷脂、用蛋白酶处理、蛋白激酶A或C磷酸化、自缔合形成寡聚体）的刺激。它是四个基因（在人类中）的产物，但额外的同工型通过可变mRNA剪接产生。大部分泵质量以三个主要单元突出到细胞质中。钙调蛋白结合结构域位于C末端突出单元。该结构域是一段约25个残基的带正电荷片段。钙激活蛋白酶钙蛋白酶通过去除其钙调蛋白结合结构域及其C末端部分来激活泵。产生的124 kDa片段已用于测试钙调蛋白结合结构域自抑制功能的建议。后者与泵的两个结构域相互作用，一个位于细胞质中部突出单元靠近活性位点处，另一个位于第一个（N末端）突出单元中。泵的同工型在调节结构域中表现出差异，例如，可变mRNA剪接可消除蛋白激酶A磷酸化的结构域，或改变泵对钙调蛋白的敏感性。这是通过在钙调蛋白结合亚结构域A和B之间插入富含组氨酸的序列来实现的。插入的结构域赋予钙调蛋白结合pH敏感性。在钙调蛋白结合结构域之前和之后的酸性区域中发现了钙结合位点。
