Mechanisms of Processivity in Molecular Motors

分子马达的过程机制

基本信息

批准号：
7437307
负责人：
STEVEN S ROSENFELD
金额：
$ 43.16万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-03-01 至 2011-02-28
项目状态：
已结题

项目摘要

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.

分子马达的过程机制肌球蛋白和驱动蛋白组成了多种分子马达，可产生力和运动以核苷酸水解为代价。尽管这两个运动超级家族几乎没有共同点一级结构中，每个组的成员通常在细胞内发挥相似的功能。例如，虽然一些肌球蛋白和驱动蛋白运输囊泡，另一些则产生维持肌球蛋白和驱动蛋白所需的皮质张力。细胞骨架和有丝分裂器。该项目的中心假设是生理学对电机的要求决定了 ff 作为酶的行为方式。因此应该可以如果已知马达在细胞内的功能，则可以预测马达酶学的关键方面。肌球蛋白 V 和传统的驱动蛋白运输囊泡的距离相对较长，并且作为孤立的单个马达工作。与中心假设一致，这两种发动机至少有一个酶学特征—— 两者都是进行性的。对于单独工作的囊泡转运蛋白来说，加工能力是必要的，因为过早解离可能会产生可怕的生理后果。因此，持续性就是一个例子电机的酶学如何通过其生理学来塑造。在这个提案中，我将扩展这个主题作为对生理需求的反应的持续性。 1将使用我用驱动蛋白生成的数据制定分子马达中的加工性如何工作的模型，并将通过比较来测试该模型特别是，我将研究分子运动酶学的三个组成部分，其对于单独工作的囊泡转运蛋白来说，其特征应该是可预测的。这些包括时间安排前进步、电机机械元件的灵活性以及变构机制沟通。总而言之，这些组件可能决定电机的处理能力，并且就像持续性本身一样，它们也应该根据生理学的要求来塑造。确定紧密程度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，这项工作将支持这样的论点：理解如何作为一种酶，运动在体外发挥作用，可以为了解它在细胞体内的运作方式提供有价值的见解。