The objectives of the subproject proposed here are to work towards developing a clearer understanding of the molecular basis for the functioning of fibrous epidermal proteins. Evidence is beginning to appear which suggests that skin diseases of various kinds, such as ichthyoses, are related to either improper folding of skin proteins, abnormal levels of their expression, sequence mutations, or some combination of all of these. Little is known of the factors that govern the association of the various skin proteins with one another, but it is becoming apparent that these interactions are critical to proper skin function and development. We seek to provide further information to clarify the manifest interaction of keratin intermediate filaments, the major epidermal cytoskeletal protein component, with filaggrin which is observedly responsible for facilitating the alignment of individual filaments into microfibril structures. We are interested identifying whether unique glycine-loop structures actually exist in keratins and the epidermal cell envelope protein loricrin, both of which are found to have the rather rare feature, among all known protein structures, of bearing extensive runs of polyglycine tandem repeats. It has been hypothesized that such loop-like structures could plausibly exist in these and a handful of other proteins. We seek to test this hypothesis further and to see, should evidence prove it true, whether such structures could underlie the unique fashion in which epidermal proteins form strong yet elastic associations with one another. Other related structural studies of skin proteins, proposed herein, have similar long- ranged objectives.
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