Emerging New Types of Motility

新兴的新型动力

• 批准号: 6940994
• 负责人: MIHALY KOVACS
• 金额: $ 5.4万
• 依托单位: EOTVOS LORAND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6940994
• 关键词: actins; biomechanics; enzyme mechanism; enzyme structure; microfilaments; muscle contraction; myosins; point mutation; protein isoforms; protein structure function; protoplasm motility

DESCRIPTION (provided by investigator): Long-term Objectives: 1. To explore new types of motility within the myosin superfamily; 2. To address fundamental unresolved issues in motor protein biochemistry such as the relation of the powerstroke to the actin binding transitions and product release steps of myosin. Significance: Motility and contractility are essential for almost all biological processes. Detailed quantitative knowledge of the enzymology of molecular motors is a prerequisite for understanding biological motility and the basis of physiological processes connected to, among others, cardiac function and malfunction, asthma, axonal regeneration and sensory illnesses. Specific Aims: 1. We will test the hypothesis that mechanical load has a functionally important effect on the product release kinetics of non-muscle myosin II; 2. We will assess if myosin X, a membrane-associated motor, has a unique mechanism of action that differs from all described types of myosin-based motility; 3. By mutational perturbation of the product release steps of myosin V, we will investigate the relation of product release to the mechanical step (powerstroke) and actin binding transitions of myosin. We will also establish the correspondence between the kinetic effects of the mutations and motility and processivity. Research Design and Methods: We will address the above questions by using single- and double-headed recombinant myosin constructs for solution kinetic, spectroscopic, biochemical and molecular mechanical investigations.

描述（由研究者提供）： 长期目标： 1.探索肌球蛋白超家族中新的运动类型; 2.解决运动蛋白生物化学中未解决的基本问题，如动力冲程与肌动蛋白结合转换和肌球蛋白产物释放步骤的关系。意义：运动性和收缩性是几乎所有生物过程所必需的。分子马达酶学的详细定量知识是理解生物运动性和与心脏功能和功能障碍、哮喘、轴突再生和感觉疾病等有关的生理过程基础的先决条件。具体目标： 1.我们将检验这一假设，即机械负荷对非肌肉肌球蛋白II的产物释放动力学具有功能上重要的影响; 2.我们将评估肌球蛋白X，一种膜相关的运动，是否具有不同于所有描述的肌球蛋白运动类型的独特作用机制; 3.通过对肌球蛋白V的产物释放步骤的突变扰动，我们将研究产物释放与肌球蛋白的机械步骤（动力冲程）和肌动蛋白结合转变的关系。我们还将建立突变的动力学效应与运动性和持续合成性之间的对应关系。 研究设计和方法： 我们将通过使用单头和双头重组肌球蛋白构建体进行溶液动力学、光谱、生物化学和分子力学研究来解决上述问题。