We have examined the oxidation-induced perturbations of calmodulin (CaM) and its interaction with the skeletal muscle ryanodine receptor (RyR1) using circular dichroism. The working hypothesis is that the detrimental effects of CaM oxidation on RyR channel regulation can be traced to definable changes in CaM structure and dynamics that result from the modification of specific methionine residues. Oxidative modification disrupts the functional CaM/RyR interaction through changes in structure and dynamics, resulting in reduced SR Ca2+ release and incomplete contractile activation.
The accumulation of oxidatively modified proteins has been implicated in the progression of biological aging, muscle degeneration and disease. Oxidative modification of muscle associated proteins
has been shown to impair skeletal muscle function in vivo and in vitro (1-5). Oxidative modification can lead to thermodynamic instability, disruption of tertiary structure, and decrease in enzymatic activity.
NIH grant to DDT (AR32961 and AG026160).
This research was also supported by the Undergraduate Research Opportunities Program (UROP).
Berglund, Andrea; Moen, Rebecca; Thomas, David.
Site-Directed Methionine Oxidation in Calmodulin.
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