Site-Directed Oxidative Modification of Muscle Protein Structural Dynamics

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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.