Site-Directed Oxidative Modification of Muscle Protein Structural Dynamics

家长补助金的长期目标是了解氧化的功能和结构后果 在肌肉蛋白中，为了阐明氧化应激影响人类健康的机制， 衰老，两个目标集中在两个关键的肌肉蛋白质-钙调蛋白和肌球蛋白。本 行政补充扩大了第二个目标，肌球蛋白，包括对动物性别差异的研究， 模型这些研究将特别关注雌激素调节翻译后的作用， 肌球蛋白的修饰。这项工作的高潜在影响是通过与一个 衰老、氧化和雌激素的小鼠模型专家。因此，这项工作开始与新的方法， 肌肉生物物理学和结构生物学在父母补助金，并增加了互补 肌肉生理学和性别差异的专业知识在合作者的实验室。这个补充项目 提供了一个独特的和创新的方法组合，都集中在一个及时的目标-解释性如何 激素，特别是研究较少的女性性激素，影响氧化和衰老的复杂效应。 肌肉蛋白质的功能、结构和动力学。

The long-term goal of the parent grant is to understand the functional and structural consequences of oxidation in muscle proteins, in order to illuminate the mechanisms by which oxidative stress affects human health and aging, with the two aims focusing on two key muscle proteins – calmodulin and myosin. The present administrative supplement extends the second aim, on myosin, to include studies on sex differences in animal models. These studies will focus particular attention on the role of estrogen modulating post-translational modifications of myosin. The high potential impact of this work is made possible by a collaboration with an expert in mouse models of aging, oxidation, and estrogen. Thus this work starts with the novel approaches of muscle biophysics and structural biology in the parent grant, and is augmented by the complementary expertise in muscle physiology and sex differences in the collaborator’s laboratory. This supplemental project offers a unique and innovative combination of approaches, all focused on a timely goal – to explain how sex hormones, particularly the less studied female sex hormone, impact the complex effects of oxidation and aging on muscle protein function, structure, and dynamics.