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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural insight into the role of myelin basic protein in multiple sclerosis
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Structural insight into the role of myelin basic protein in multiple sclerosis

机译：对髓磷脂碱性蛋白在多发性硬化中的作用的结构性认识

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In the article by Musse et al. in this issue of PNAS (1), the authors present unique and compelling physico-chemical data that demonstrate the structural instability of myelin in multiple sclerosis (MS). Such alteration in myelin stability, reported as secondary to changes in myelin basic protein (MBP) structure, may be causative in nature and/or contribute to the early course of demyelination in MS. A combination of physico-chemical and theoretical approaches enabled the authors to arrive at their conclusions and demonstrated that myelin structural information can shed light on mechanistic dysfunction in MS. The primary findings are that an altered charge isomer of MBP (rmC8) that is associated with disease severity in MS (2) has less membrane depth penetration and shorter α-helix structure, making the immunodominant epitope of this protein more exposed to the cy-tosolic space and readily digested by proteases. This change in MBP conformation would free the epitope for T cell recognition and suggests a mechanism of action potentially initiated by alterations in myelin structure. This hypothesis is supported by a recent study describing antibody enzymes (abzymes) that catalyze MBP in a site-specific degradation (3). The C8 MBP isoform is also more abundant in immature myelin, and results of this study support the hypothesis that myelin structure in MS is developmentally immature (4), contributing to altered myelin stability and possibly the initiation of the disease.
机译：在Musse等人的文章中。在本期PNAS（1）中，作者提出了独特而引人注目的理化数据，证明了多发性硬化症（MS）中髓磷脂的结构不稳定性。据报道，髓磷脂稳定性的这种改变是髓鞘碱性蛋白（MBP）结构变化的继发性改变，在本质上可能是致病性的和/或有助于MS脱髓鞘的早期过程。物理化学和理论方法的结合使作者能够得出结论，并证明髓鞘结构信息可以阐明MS的机械功能障碍。主要发现是，与MS中的疾病严重程度相关的MBP（rmC8）电荷异构体的改变（2）具有较小的膜深度渗透和较短的α-螺旋结构，从而使该蛋白的免疫优势表位更多地暴露于cy-的空间和容易被蛋白酶消化。 MBP构象的这种变化将释放表位供T细胞识别，并提示可能由髓磷脂结构改变引发的作用机制。最近的一项研究支持了这一假设，该研究描述了可在位点特异性降解中催化MBP的抗体酶（抗体酶）（3）。 C8 MBP亚型在未成熟的髓磷脂中也更为丰富，这项研究的结果支持以下假设：MS中的髓磷脂结构在发育上不成熟（4），这有助于改变髓磷脂的稳定性，并可能引发疾病。

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