TorsinA是位于细胞内质网腔的一种ATP酶，其C端一个谷氨酸残基的缺失会导致早发型全身性肌张力障碍（early-onset primary torsion dystonia，EOPTD）。这是一种可遗传的神经性运动障碍，患者因身体肌肉的持续收缩而无法随意活动。根据同源性分析，torsinA属于AAA+蛋白超家族，通过水解ATP产生的能量使其底物发生构象变化，参与细胞内多种重要过程，已发现几种与其发生相互作用的蛋白质，但作用机制不详。本研究计划运用X-射线晶体学结合核磁共振波谱学解析torsinA与其相互作用蛋白质的结构，并研究二者结合引起的构象变化；运用生物化学和细胞生物学方法验证torsinA与不同底物蛋白质的相互作用，特别是它们在细胞迁移中的作用，分析突变体的影响。期望在分子水平上阐述torsinA发挥功能的结构基础，为认识EOPTD的致病机理和发展有效治疗方法提供理论依据。

TorsinA is a novel ATPase localized within the lumen of the endoplasmic reticulum (ER). A deletion of one of a pair of glutamate residues (E302/303) near the carboxyl-terminus of torsinA causes most cases of early-onset primary torsion dystonia (EOPTD). EOPTD is an inherited neurological movement disorder that causes the muscles to contract involuntarily，forcing the body of patients into repetitive movements and often twisted postures. Homologous sequence analysis reveals that torsinA is a member of AAA+ ATPase superfamily of proteins (the ATPases associated with a variety of cellular activities), which have a variety of cellular locations and functions. Description of the structure and the function of torsinA is the most basic step in elaborating a molecular mechanism of EOPTD which can be exploited for therapeutic benefit. Utilizing X-ray crystallography and NMR, we are planning to solve the structure of torsinA and its interacting proteins, study the conformational changes of the interaction between them. In addition, we are going to investigate the physiological functions of torsinA and its interacting proteins, especially their roles in cell migration in various neurons, and the dysfunction of the known dystonia-causing mutations, for better understanding the molecular pathology of EOPTD.