Mechanisms of Processivity in Molecular Motors

分子马达中的加工能力机制 肌球蛋白和驱动蛋白组成了一个多样化的分子马达的集合，产生力和运动 以核苷酸水解为代价。尽管这两个汽车超级家族几乎没有共同点， 在一级结构中，每个组的成员通常在细胞内发挥相似的功能。例如尽管 一些肌球蛋白和驱动蛋白运输囊泡，另一些产生皮质张力，维持皮质张力。 细胞骨架和有丝分裂器。该项目的中心假设是， 对马达的要求决定了FF作为酶的行为。因此，应该能够 如果细胞内的功能是已知的，预测运动酶学的关键方面。肌球蛋白V和 传统的驱动蛋白运输囊泡相对较长的距离，并作为单独的马达工作。 与中心假设一致，这两个马达至少有一个共同的酶学特征， 两者都是渐进的。对于单独工作的囊泡转运蛋白来说，持续合成能力是必要的，因为 过早分离会有可怕的生理后果。因此，持续合成能力可以作为一个例子 运动的酶学是如何被生理学塑造的。在本提案中，我将对这一主题进行扩展 是对生理需求的反应。1将使用我用驱动蛋白生成的数据， 制定了一个模型，如何在分子马达的持续加工工作，并将测试这个模型，通过比较 特别是，我将研究分子运动酶学的三个组成部分， 对于孤立工作的囊泡转运蛋白，其特征应该是可预测的。这些问题包括 向前的一步，电机的机械元件的灵活性，和变构机制， 通信综合起来，这些组成部分可能决定了运动的进行性， 就像持续性本身一样，它们也应该由生理需求来塑造。决定了 这些成分符合基于生理学的预测，因此将提供对 中心假设此外，如果成功的话，这项工作将支持这样一个论点，即理解一个人是如何 马达在体外作为一种酶工作可以提供有价值的见解，了解它如何在体内细胞中工作。

Mechanisms of Processivity in Molecular Motors Myosins and kinesins make up a diverse collection of molecular motors that generate force and movement at the expense of nucleotide hydrolysis. Despite the fact that these two motor superfamilies share little primary structure, members of each group often serve similar functions within the cell. For example, while some myosins and kinesins transport vesicles, others generate the cortical tension required to maintain the cytoskeleton and the mitotic apparatus. The central hypothesis of this project is that the physiologic demands placed on a motor determine how ff behaves as an enzyme. It should therefore be possible to predict key aspects of a motor's enzymology if its function within the cell is known. Myosin V and conventional kinesin transport vesicles relatively long distances and work as single motors in isolation. Consistent with the central hypothesis, these two motors share at least one feature of their enzymology-- both are processive. Processivity would be necessary for vesicle transporters that work in isolation, since premature dissociation could have dire physiologic consequence. Thus, processivity serves as an example of how a motor's enzymology can be shaped by its physiology. In this proposal, I will expand on this theme of processivity as a response to physiologic demands. 1will use the data I have generated with kinesin to formulate a model of how processivity works in molecular motors, and will test this model by comparing kinesin to myosin V. In particular, I will examine three components of molecular motor enzymology whose features should be predictable for vesicle transporters that work in isolation. These include the timing of the forward step, the flexibility of the motor's mechanical element, and the mechanism of allosteric communication. Taken together, these components are likely to determine how processive a motor is, and like processivity itself, they too should be shaped by the demands of physiology. Determining how closely these components conform to the predictions based on physiology will therefore provide a critical test of the central hypothesis. Furthermore, if successful, this work will support the argument that understanding how a motor works in vitro as an enzyme can provide valuable insights into how it works in vivo in the cell.