STRUCTURAL ANALYSIS OF DAX1

描述：(摘自申请者的摘要)肾上腺发育和肾上腺发育的潜在原因仍未完全了解。这项提议的具体目的是为了提高对这些过程的分子机制的了解。DAX1蛋白是肾上腺发育的关键效应因子，当其表达被破坏时，X连锁肾上腺发育不良先天畸形的发生就是明证。通过使用体外表达的DAX1，将有可能获得对蛋白质结构的高分辨率结晶学分析。这一分析将通过定义蛋白质的结构组织和与DAX1突变的已知后果相关的结构，从而深入了解DAX1的发育。通过使用这种结构知识来预测DAX1上与伙伴蛋白相互作用的位点，并使用这些预测来分离这些伙伴，将获得进一步的见解。通过更清楚地阐明DAX1在肾上腺发育中的作用，这些研究结果将有助于肾上腺发育障碍的诊断和治疗，如先天性肾上腺发育不良。

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.