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,

说明. 这项研究的长期目标是提供一个更好的 了解细胞内细胞器沿着运动的机制 这种运动在快速的过程中起着特殊的作用。 神经细胞中的轴突运输。 这一过程提供了一种手段， 新合成的物质从它们的合成位置移动到 神经细胞体与轴突末端的突触相连。 驱动蛋白具有 广泛存在于高等真核生物中， 类型，而不仅仅是神经元。 在这些其他类型的细胞中，驱动蛋白可能 负责某些类型的膜囊泡的相关运输 朝向细胞的外围。 其他蛋白质与 驱动蛋白负责沿着纺锤体微管的部分运动 在细胞分裂期间。 拟议研究中开发的信息还将 也适用于其他重要的马达蛋白。 驱动蛋白运动的能量由水解提供 三磷酸腺苷（ATP）。 拟议工作的一个主要目标是 重点确定ATP水解的详细酶促机理 关于水解的化学能量变化是如何与物理能量变化相结合的， 产生沿微管的沿着运动。 因为运动的结果 从酶构象的变化，也很重要的是， 了解酶的结构及其在催化过程中的变化。 一个正在进行的方法是表征的个别域的 驱动蛋白 最近的进展表明，驱动蛋白在体内被折叠成一种具有生物活性的蛋白质。 被抑制的形式，需要展开之前，它可以是一个积极的马达。 的 折叠是由两个末端的区域相互作用产生的。 蛋白质折叠过程及其调控因素的研究 影响它将被执行。 将广泛使用稳定和 单周转动力学的机制的调查。 这些 酶的研究将与运动性的研究相结合， 能够生产。 一个长期目标是能够模拟物理 驱动蛋白的性质基于其溶液生化机制，