STRUCTURAL ANALYSIS OF DAX1

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DESCRIPTION: (Scanned from the applicant's abstract) Both adrenal development and underlying causes of developmental adrenal remain incompletely understood. The specific aims of this proposal are designed to improve knowledge of the molecular mechanisms of these processes. The DAX1 protein is key effector of adrenal development, as evidenced by the occurrence of X-linked adrenal hypoplasia Congenita when its expression is disrupted. Through use of in vitro expressed DAX1, it will be possible to obtain high resolution crystallographic analysis of the structure of the protein. This analysis will allow insights into the developmental of DAX1 by defining the structural organization of the protein and related structure to the known consequences of DAX1 mutation. Further insights will be gained through the use of this structure knowledge to predict sites on DAX1 that interact with partner proteins, and to use these predictions to isolate these partners. By elucidating more clearly the role of DAX1 in adrenal development, the results of these studies will facilitate the diagnosis and treatment of development adrenal dysfunction, such as Adrenal Hypoplasia Congenita.