质膜钙泵的刺激和活性理论
A theory of Plasma Membrane Calcium Pump stimulation and activity
摘要：
ATP驱动的质膜钙泵或Ca（2+）-ATP酶（PMCA）的特征在于与其他跨膜钙转运蛋白相比对钙的高亲和力和低转运速率。它对细胞的钙排出起着至关重要的作用。钙调素是一种细胞内钙缓冲蛋白，其能够以其Ca（2+）配体形式通过增加对钙的亲和力和最大钙转运速率来刺激PMCA。我们引入了一个新的模型，这个刺激过程，并推导出实验观测值的解析表达式，以确定模型参数的基础上，具体的实验。此外，我们开发了一个模型的泵送活动。泵的描述解决了在易位步骤中Ca（2+）：ATP化学计量比为1：1的表面矛盾，以及泵在细胞内位点结合两个钙离子的观察结果。钙泵和刺激模型的组合正确描述了PMCA功能。我们发现，钙调素-钙复合物附着到泵和刺激的过程必须分开。其他PMCA属性的模型的框架中进行了讨论。所提出的模型可以作为一种工具，钙动力学模拟，并提供了可能性，以不同的泵异构体的不同类型的特定参数集。
英文摘要：
The ATP-driven Plasma Membrane Calcium pump or Ca(2+)-ATPase (PMCA) is characterized by a high affinity to calcium and a low transport rate compared to other transmembrane calcium transport proteins. It plays a crucial role for calcium extrusion from cells. Calmodulin is an intracellular calcium buffering protein which is capable in its Ca(2+) liganded form of stimulating the PMCA by increasing both the affinity to calcium and the maximum calcium transport rate. We introduce a new model of this stimulation process and derive analytical expressions for experimental observables in order to determine the model parameters on the basis of specific experiments. We furthermore develop a model for the pumping activity. The pumping description resolves the seeming contradiction of the Ca(2+):ATP stoichiometry of 1:1 during a translocation step and the observation that the pump binds two calcium ions at the intracellular site. The combination of the calcium pumping and the stimulation model correctly describes PMCA function. We find that the processes of calmodulin-calcium complex attachment to the pump and of stimulation have to be separated. Other PMCA properties are discussed in the framework of the model. The presented model can serve as a tool for calcium dynamics simulations and provides the possibility to characterize different pump isoforms by different type-specific parameter sets.
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