Functional Dynamics of the Myosin Molecular Motor

肌球蛋白分子马达的功能动力学

• 批准号: 7077227
• 负责人: YURI NESMELOV
• 金额: $ 10.63万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7077227
• 关键词: Gastropoda; actins; biophysics; myosins; nucleotides; training

DESCRIPTION (provided by applicant): The applicant, Dr. Yuri E. Nesmelov, is a physicist whose research has focused on the interaction of electromagnetic fields with matter. Dr. Nesmelov proposes to learn and utilize molecular biophysical and biochemical techniques to round out a multidisciplinary approach to be used in studying myosin functional dynamics. Career Development/Training Plan: The primary element of the plan will be the acquisition of advanced molecular biophysical and biochemical techniques from mentored training. The majority of the training will come from the primary mentor, Dr. David D. Thomas, who is an internationally known scientist in the field of muscle biophysics, and is the director of an NIH-funded training program in muscle research. Additional training in cell and molecular biology will be provided by the co-mentor, Dr. Margaret Titus, who is well known for her work on myosin. Part of the research (W band electron paramagnetic resonance (EPR)) will be performed with a collaborator, Dr. Peter Fajer, a renowned specialist in biological EPR and muscle biophysics. Structured activities for further career and research development will include attendance and participation at national scientific meetings, regular involvement in journal clubs and seminars, and affiliation with the Muscular Dystrophy Center at the University of Minnesota. Research Plan: The overall aim of this proposal is for Dr. Nesmelov to learn molecular biophysical and biochemical techniques and apply them together with site-directed spin labeling and multifrequency EPR spectroscopy, to explore internal dynamics of myosin motor functioning. The proposed work is based on recent developments by the applicant in sensitivity improvement for EPR measurement, especially for experiments on myosin in solution, and in multifrequency EPR data analysis, to accurately characterize the dynamics of a proteinbound spin label. This approach will be used to obtain detailed information about the dynamic rearrangement of protein structural elements. These methods will be developed further, and used to define the kinetics of structural rearrangements of the relay helix and SH1 helix in myosin during the actomyosin ATPase cycle.

描述（由申请人提供）：申请人 Yuri E. Nesmelov 博士是一位物理学家，其研究重点是电磁场与物质的相互作用。 Nesmelov 博士建议学习和利用分子生物物理和生物化学技术来完善用于研究肌球蛋白功能动力学的多学科方法。职业发展/培训计划：该计划的主要内容是从指导培训中获取先进的分子生物物理和生化技术。大部分培训将来自主要导师 David D. Thomas 博士，他是肌肉生物物理学领域的国际知名科学家，也是 NIH 资助的肌肉研究培训项目的主任。共同导师 Margaret Titus 博士将提供细胞和分子生物学方面的额外培训，她因肌球蛋白方面的研究而闻名。该研究的一部分（W 波段电子顺磁共振 (EPR)）将与生物 EPR 和肌肉生物物理学领域的著名专家 Peter Fajer 博士合作进行。进一步职业和研究发展的结构化活动将包括出席和参加国家科学会议、定期参加期刊俱乐部和研讨会以及加入明尼苏达大学肌肉萎缩症中心。研究计划：该提案的总体目标是让 Nesmelov 博士学习分子生物物理和生化技术，并将其与定点自旋标记和多频 EPR 光谱一起应用，以探索肌球蛋白运动功能的内部动力学。所提出的工作基于申请人在 EPR 测量灵敏度改进方面的最新进展，特别是溶液中肌球蛋白的实验，以及多频率 EPR 数据分析，以准确表征蛋白质结合自旋标签的动态。该方法将用于获得有关蛋白质结构元件动态重排的详细信息。这些方法将得到进一步开发，并用于定义肌球蛋白 ATP 酶循环期间肌球蛋白中中继螺旋和 SH1 螺旋结构重排的动力学。