Three-dimensional structure of the major autoantigen in primary biliary cirrhosis
Three-dimensional structure of the major autoantigen in primary biliary cirrhosis
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DOI：
10.1016/s0016-5085(98)70375-0
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发表时间：
1998-07-01
期刊：
影响因子：
29.4
通讯作者：
Yeaman, SJ
中科院分区：
文献类型：
--
作者：
Howard, MJ;Fuller, C;Yeaman, SJ
背景和目标：原发性胆汁性肝硬化（PBC）是一种慢性胆汁淤积性肝病，其特征是患者血清中存在抗线粒体自身抗体。由来自>95%的PBC患者的抗体识别的主要自身抗原已被鉴定为丙酮酸脱氢酶多酶复合物的E2组分（E2p）。E2p上的免疫显性位点已定位于两个硫辛酰基结构域的内部，其中必需辅因子硫辛酸共价连接。本研究的目的是确定人E2p的内部硫辛酰结构域的三维结构。方法：在大肠杆菌中表达该结构域，纯化后用核磁共振波谱分析其结构。结果如下：从人E2p的硫辛酰结构域的结构进行了测定，并评估了自身免疫识别的结构的影响。结论：结构的知识进一步定义了主要表位，并可能有助于设计用于治疗PBC的抗原特异性免疫疗法。
Background & Aims: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. The major autoantigen, recognized by antibodies from >95% of patients with PBC, has been identified as the E2 component (E2p) of the pyruvate dehydrogenase multienzyme complex, Immunodominant sites on E2p have been localized to the inner of the two lipoyl domains, where the essential cofactor lipoic acid is attached covalently. The aim of this study was to determine the three-dimensional structure of the inner lipoyl domain of human E2p. Methods: The domain was expressed in Escherichia coli; after purification, its structure was analyzed using nuclear magnetic resonance spectroscopy. Results: The structure of the lipoyl domain from human E2p was determined, and the implications of the structure for autoimmune recognition were assessed. Conclusions: Knowledge of the structure further defines the major epitope and may help in the design of antigen-specific immunotherapy for treatment of PBC.