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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis
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The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis

机译：髓磷脂少突胶质细胞糖蛋白的晶体结构，多发性硬化症的关键自身抗原

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摘要

Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary clemyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopathological role of MOG, we determined the 1.8-Angstrom crystal structure of the MOG extracellular domain (MOG(ED)). MOG(ED) adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel head-to-tail dimer. A dimeric form of native MOG was observed, and MOGED was also shown to dimerize in solution, consistent with the view of MOG acting as a homophilic adhesion receptor. The MOG(35-55) peptide, a major encephalitogenic determinant recognized by both T cells and demyelinating autoantibodies, is partly occluded within the dimer interface. The structure of this key autoantigen suggests a relationship between the dimeric form of MOG within the myelin sheath and a breakdown of immunological tolerance to MOG that is observed in multiple sclerosis. [References: 36]
机译：髓磷脂少突胶质细胞糖蛋白（MOG）是多发性硬化症中主要的髓鞘形成的关键CNS特异性自身抗原。尽管已经确定了MOG的致病作用，但其在CNS中的确切功能仍然不清楚。为了获得对MOG的生理和免疫病理作用的新见解，我们确定了MOG细胞外域（MOG（ED））的1.8埃晶体结构。 MOG（ED）采用经典的Ig（Ig可变域）折叠，观察到它形成反平行的头对尾二聚体。观察到天然MOG的二聚体形式，并且MOGED还显示出在溶液中二聚，这与MOG作为同型粘附受体的观点一致。 MOG（35-55）肽是T细胞和脱髓鞘自身抗体都能识别的主要致脑细胞决定簇，部分被二聚体界面封闭。该关键自身抗原的结构表明髓鞘内的MOG的二聚体形式与多发性硬化症中观察到的对MOG的免疫耐受性下降之间存在关联。 [参考：36]

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