Browsing by Author "Crain, Jonathan"
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Item Conformational changes in actinin-type actin binding domains: probing actin-induced structural dynamics in dystrophin and utrophin using EPR spectroscopy.(2014-12) Crain, JonathanThe underlying cause of Duchenne and Becker muscular dystrophies is a lack of functional dystrophin, a large multidomain protein. Dystrophin is normally expressed in muscle, where it links the extracellular matrix to the cortical actin cytoskeleton via a complex of associated proteins. Dystrophin, and its autosomal homologue utrophin, connect with the actin cytoskeleton through two F-actin binding domains, including an N-terminal "actinin-type" actin binding domain (ABD).In addition to dystrophin and utrophin, actinin-type ABDs are found in a large number of proteins. Nonetheless, the actin binding mechanism remains poorly understood: x-ray crystallography and electron microscopy have produced conflicting models. Electron paramagnetic resonance (EPR) spectroscopy, especially double electron-electron resonance (DEER), can be used to distinguish between these models or to build new models. In this thesis, I present data from DEER experiments which suggest that actinin-type ABDs of dystrophin and utrophin adopt unexpected conformations in solution.