Structural Dynamics Of Actomyosin Motility

肌动球蛋白运动的结构动力学

基本信息

  • 批准号:
    7528513
  • 负责人:
  • 金额:
    $ 47.49万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1980
  • 资助国家:
    美国
  • 起止时间:
    1980-04-01 至 2012-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The overall aims of this research are to understand the molecular mechanism by which actomyosin motility systems convert chemical energy into mechanical work, and to obtain a precise correlation between the mechanical, biochemical and structural events at the molecular level. Novel methods will be applied to isolated muscle myosin and unconventional myosin molecular motors to probe the relations between biochemical reactions of the contractile proteins, the elementary mechanical steps of the cross-bridge cycle and the corresponding structural motions. Bifunctional or bi-arsenical fluorescent probe molecules will be stably bound with known orientation to the motor domains and to light chain subunits in the myosin heads. The spatial orientation and translational position of these components will be monitored at high time resolution by novel single-molecule fluorescence polarization, total internal reflection (polTIRF) microscopy to determine the dynamics of specific protein structural changes. Increased time resolution of the rotational and translational motions will enable events during molecular steps to be determined. Nanometer resolution tracking of the molecular position in the x, y and z directions, using a new "Parallax View" technique will disclose mechanisms of molecular stepping and choice of path along the cytoskeletal filament. An infrared optical trap, with high-speed feedback to clamp the actin in place, will be combined with single-molecule polTIRF microscopy to directly evaluate the influence of mechanical stress and strain on stepping rates and protein orientation changes that relate to chemo-mechanical transduction. The energetics and probabilistic nature of stepping target selection will be determined from the orientation and force dependence of the distributions of head angle, biochemical state and step size. The experiments will be carried out on conventional myosin isolated from muscle tissue and on non-muscle myosins isolated from neural tissue and recombinant expression systems. Results from this project should significantly advance knowledge of cell motility processes and thus bring a greater understanding of both normal and pathological states of striated muscle, neuronal development and other types of cell motility. PUBLIC HEALTH RELEVANCE: Myosin molecular motors are involved, altered or compromised in many diseases, such as muscle weakness and fatigue, hypertrophic cardiomyopathy, hypertension, cell division, chemotaxis, neoplastic invasiveness and metastasis, and in many neurological diseases, such as specific forms of developmental deficits and congenital deafness and blindness. Fundamental research on these proteins thus will provide the basic understanding to enable generation of new diagnostic and therapeutic measures.
描述(由申请人提供):这项研究的总体目的是了解肌动球蛋白运动系统将化学能转化为机械工作的分子机制,并在分子水平上获得机械,生化和结构事件之间的精确相关性。新方法将应用于分离的肌肉肌球蛋白和非常规肌球蛋白分子电机,以探测收缩蛋白的生化反应,跨桥循环的基本机械步骤与相应的结构运动之间的关系。双功能或双疗法荧光探针分子将稳定地结​​合到运动结构域和肌球蛋白头中的轻链亚基。这些组件的空间取向和平移位置将通过新型的单分子荧光偏振,总内反射(POLTIRF)显微镜在高时间分辨率下监测,以确定特定蛋白质结构变化的动力学。旋转和翻译运动的时间分辨率增加将使在分子步骤中确定事件。使用新的“视差视图”技术,分子位置在X,Y和Z方向上的纳米分辨率跟踪将披露分子步进的机制和沿细胞骨架细丝的路径的选择。具有高速反馈以将肌动蛋白固定到位的红外光学陷阱将与单分子Poltirf显微镜结合使用,以直接评估机械应力和对培养率和蛋白质方向变化的影响,这些变化与化学机械转导有关。步进目标选择的能量和概率性质将取决于头角,生化状态和步长的分布的方向和力依赖性。实验将对从肌肉组织分离的常规肌球蛋白以及从神经组织和重组表达系统中分离出来的非肌肉肌球蛋白。该项目的结果应显着提高细胞运动过程的知识,从而使对横纹肌肉,神经元发育和其他类型的细胞运动的正常状态和病理状态有更深入的了解。公共卫生相关性:肌球蛋白分子电机在许多疾病中都参与,改变或妥协,例如肌肉无力和疲劳,肥厚型心肌病,高血压,细胞分裂,趋化性,肿瘤的侵入性和转移,以及许多神经系统疾病,以及许多神经系统疾病,例如发育性的特定形成型和康型性的表现性和康型性表现力性和副异型性。因此,对这些蛋白质的基本研究将提供基本的理解,以产生新的诊断和治疗方法。

项目成果

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YALE E GOLDMAN其他文献

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{{ truncateString('YALE E GOLDMAN', 18)}}的其他基金

Mechanochemistry of myosin mutations that cause cardiomyopathy
导致心肌病的肌球蛋白突变的机械化学
  • 批准号:
    10624860
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
Mechanochemistry of myosin mutations that cause cardiomyopathy
导致心肌病的肌球蛋白突变的机械化学
  • 批准号:
    10230396
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
Mechanochemistry of myosin mutations that cause cardiomyopathy
导致心肌病的肌球蛋白突变的机械化学
  • 批准号:
    10413088
  • 财政年份:
    2021
  • 资助金额:
    $ 47.49万
  • 项目类别:
Structural Dynamics of Molecular Motors and the Ribosome
分子马达和核糖体的结构动力学
  • 批准号:
    10166635
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
"Structural Dynamics of Molecular Motors and the Ribosome" The studies proposed will give basic information on gene expression, cellular development, and transport motor function in cell biology.
“分子马达和核糖体的结构动力学” 拟议的研究将提供细胞生物学中基因表达、细胞发育和运输马达功能的基本信息。
  • 批准号:
    10988683
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Structural Dynamics of Molecular Motors and the Ribosome
分子马达和核糖体的结构动力学
  • 批准号:
    10469325
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Structural Dynamics of Molecular Motors and the Ribosome
分子马达和核糖体的结构动力学
  • 批准号:
    10620793
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Structural Dynamics of Molecular Motors and the Ribosome
分子马达和核糖体的结构动力学
  • 批准号:
    9566213
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Structural Dynamics of Molecular Motors and the Ribosome
分子马达和核糖体的结构动力学
  • 批准号:
    9315836
  • 财政年份:
    2016
  • 资助金额:
    $ 47.49万
  • 项目类别:
Regulations and Interactions amoung Molecular Motors
分子马达之间的调节和相互作用
  • 批准号:
    7691972
  • 财政年份:
    2009
  • 资助金额:
    $ 47.49万
  • 项目类别:

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识别和验证细胞壁合成途径中的新抗生素靶标
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