髓鞘少突胶质细胞糖蛋白的晶体结构，多发性硬化症中的一种关键自身抗原。
The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis.
作者信息
Clements Craig S, Reid Hugh H, Beddoe Travis, Tynan Fleur E, Perugini Matthew A, Johns Terrance G, Bernard Claude C A, Rossjohn Jamie
机构信息
Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3168, Australia.
出版信息
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11059-64. doi: 10.1073/pnas.1833158100. Epub 2003 Sep 5.
Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination 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-A crystal structure of the MOG extracellular domain (MOGED). MOGED 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 MOG35-55 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.
髓鞘少突胶质细胞糖蛋白（MOG）是多发性硬化症原发性脱髓鞘的关键中枢神经系统特异性自身抗原。尽管MOG的致病作用已经明确，但其在中枢神经系统中的精确功能仍不清楚。为了深入了解MOG的生理和免疫病理作用，我们测定了MOG细胞外结构域（MOGED）的1.8埃晶体结构。MOGED采用经典的免疫球蛋白（Ig可变结构域）折叠，观察到其形成反平行的头对头二聚体。观察到天然MOG的二聚体形式，并且MOGED在溶液中也显示出二聚化，这与MOG作为同嗜性粘附受体的观点一致。MOG35-55肽是T细胞和脱髓鞘自身抗体识别的主要致脑炎决定簇，部分被包埋在二聚体界面内。这种关键自身抗原的结构表明，髓鞘内MOG的二聚体形式与多发性硬化症中观察到的对MOG免疫耐受的破坏之间存在关联。
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