STRUCTURAL STUDIES ON MOLECULAR TRACKS AND MOTORS

分子轨道和马达的结构研究

• 批准号: 6497408
• 负责人: RONALD A MILLIGAN
• 金额: $ 30.63万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6497408
• 关键词: Acanthamoeba; Dictyostelium; actins; calmodulin; cell motility; chickens; conformation; cryoelectron microscopy; dynein ATPase; gold; image processing; imaging /visualization /scanning; laboratory rabbit; molecular dynamics; myosins; phosphorylation; protein structure function; smooth muscle; structural biology

DESCRIPTION: The interactions of molecular tracks and motors result in movements in cells. Fundamental to our understanding of the way in which motility is accomplished in cells is a detailed description not only of the atomic structures of the complexes involved, but also the way in which the activity of these complexes is regulated in response to the needs of the cell. The long term goals of the work described in this application are to understand in structural terms, the way in which myosin motors are regulated. Three types of myosin-based regulation will be investigated: (I) Regulation mediated by light chain phosphorylation will be investigated by examining a number of smooth muscle myosin constructs. (ii) Regulation by light chain dissociation will be examined in brush border myosin l and myosin V. (iii) Regulation by heavy chain phosphorylation will be investigated in Acanthamoeba and Dictyostelium myosin ls. The methods to be used include cryoelectron microscopy, helical image analysis and modeling using the x-ray structures of the myosin head and regulatory domain. The experiments have been designed to visualize actomyosin conformations which are the basis of the regulatory mechanism. Atomic models of the regulated and activated states will be built from the EM and X-ray data. The results should provide detailed insights into the structural basis for regulation in myosin involved in uterine contractions, blood pressure maintenance and intestinal peristalsis (smooth muscle myosin), and in intracellular trafficking and endocytosis (myosin ls and Vs). Some exploratory experiments on dynein are planned.

描述：分子轨道和电动机的相互作用导致 细胞中的运动。 我们对理解方式的基础 在单元格中完成运动性不仅是 涉及综合体的原子结构，也是 这些配合物的活性是根据需求调节的 细胞。 本应用程序中描述的工作的长期目标是 从结构上理解肌球蛋白电机的方式 受监管。 将研究三种基于肌球蛋白的法规：（i）法规 通过轻链磷酸化介导的 平滑肌肌球蛋白构建体的数量。 （ii）通过轻链调节 解离将在刷边界肌球蛋白L和肌球蛋白V中检查。（iii） 通过重链磷酸化调节将在 Acanthamoeba和dictyostelium肌球蛋白LS。 要使用的方法包括冷冻电子显微镜，螺旋图像 使用肌球蛋白头的X射线结构进行分析和建模 监管域。 实验已设计为可视化 肌动球蛋白构象是调节机制的基础。 受监管和激活状态的原子模型将由 EM和X射线数据。 结果应提供详细的见解 肌球蛋白涉及子宫收缩的结构基础， 血压维持和肠蠕动（平滑肌 肌球蛋白），以及细胞内贩运和内吞作用（肌球蛋白LS和 vs）。 计划了一些关于动力蛋白的探索性实验。