MECHANISM OF KINESIN ATPASE

驱动蛋白ATP酶的机制

• 批准号: 2488167
• 负责人: DAVID Daniel HACKNEY
• 金额: $ 24.62万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2488167
• 关键词: active sites; adenosine triphosphate; adenosinetriphosphatase; cell motility; chemical kinetics; conformation; dimer; enzyme mechanism; enzyme structure; high energy compound; hydrolysis; intracellular transport; kinesin; microtubules; mutant; protein folding; protein isoforms; vesicle /vacuole

DESCRIPTION. The long range goal of this research is to provide a better understanding of the mechanism of movement of intracellular organelles along microtubules, Such movement plays a special role in the process of fast axonal transport in nerve cells. This process provides one means for the movement of newly synthesized material from their site of synthesis in the body of a nerve cell to the synapse at the end of the axon. Kinesin has been found in a wide range of higher eukaryotes and are present in most cell types, not just neurons. In these other cell types, kinesin is likely responsible for the related transport of some classes of membrane vesicle towards the periphery of the cell. Other proteins that are related to kinesin are responsible for part of the movement along spindle microtubules during cell division. Information developed in the proposed study will also be applicable to these other important motor proteins. The energy that drives the movement of kinesin is provided by the hydrolysis of adenosine triphosphate (ATP). A principal aim of the proposed work is to determine the detailed enzymatic mechanism of ATP hydrolysis with emphasis on how the chemical energy change of hydrolysis is coupled to the physical generation of movement along a microtubule. Because the movement results from changes in the conformation of the enzyme, it is also important to understand the structure of the enzyme and how it changes during catalysis. One ongoing approach is characterization of the individual domain of kinesin. Recent progress indicates that kinesin is folded in vivo into an inhibited form that needs to unfold before it can be an active motor. The folding is produced by the interaction of regions in the two ends of the protein and the study of the regulation of the folding process and factors influencing it will be performed. Extensive use will be made of steady and single turnover kinetics in the investigation of the mechanism. These enzymatic studies will be coupled with study of the motility that kinesin is able to produce. A long range goal is to be able to model the physical properties of kinesin based on its solution biochemical mechanism,

描述。 这项研究的远距离目标是提供更好的 了解细胞内细胞器运动机理 微管，这种运动在快速过程中起着特殊的作用 神经细胞中的轴突运输。 这个过程为 新合成材料从其合成部位移动 神经细胞的身体在轴突末端到突触。 动力蛋白具有 发现在广泛的较高的真核生物中，并且存在于大多数细胞中 类型，而不仅仅是神经元。 在这些其他细胞类型中，可能 负责某些类别的膜囊泡的相关运输 朝向细胞的外围。 与 驱动蛋白负责沿纺锤微管运动的一部分 在细胞分裂期间。 在拟议的研究中开发的信息也将 适用于这些其他重要的运动蛋白。 驱动驱动蛋白运动的能量由水解提供 三磷酸腺苷（ATP）。 拟议工作的主要目的是 确定ATP水解的详细酶促机制重点 关于水解的化学能变化如何与物理耦合 沿着微管的运动产生。 因为运动结果 从酶构象的变化中，对于 了解酶的结构及其在催化过程中的变化。 一种持续的方法是表征的单个领域 动力学。 最近的进度表明，驱动蛋白在体内折叠成一个 抑制形式需要展开，然后才能成为主动电动机。 这 折叠是由区域在两端的两端的相互作用产生的 蛋白质和折叠过程调节的研究和因素 影响它将进行。 广泛使用将是稳定的，并且 在调查机制中的单个失误动力学。 这些 酶促研究将与驱动蛋白是动力学的研究相结合 能够生产。 一个远距离目标是能够建模物理 驱动蛋白基于其溶液的生化机制的特性，