远位免疫球蛋白M核心的结构提供了关于聚合物抗体进化,组装和功能的见解
Mengfan Lyu1, Andrey G Malyutin2,3,4, Beth M Stadtmueller5,6,7,8
1Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA.
Nature communications
|November 22, 2023
概括
研究人员确定了teleost IgM的结构,揭示了四个IgM的独特组合,没有连接链. 这一发现突显了聚合物免疫球蛋白结构及其功能多样化的演变.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 进化生物学 进化生物学
背景情况:
- 聚合物免疫球蛋白 (pIgs) 对于脊椎动物的免疫反应至关重要.
- pIgs通常由26的Ig单体组成,通常与连接链 (JC) 相关联.
- 猪的结构和JC包含在物种和重链类别之间有很大差异.
研究的目的:
- 阐明远距离IgM (tIgM) 的三维结构.
- 了解在缺乏连接链的物种中tIgM的组装机制.
- 将tIgM的结构组织与哺乳动物IgM进行比较.
主要方法:
- 使用冷电子显微镜来确定远距离IgM的结构.
- 进行了突变分析,以调查结构发现的功能影响.
主要成果:
- 低温电子显微镜结构揭示了由四个由八个C端尾部 (Tps) 连接的IgM Fcs组成的远端IgM.
- 尾部形成了一个独特的β-三明治类域 (Tp组件),位于两个Fcs之间.
- 两个重链表现出独特的折叠模式,将tIgM与典型的五个单质哺乳动物IgM结构区分开来.
结论:
- 与哺乳动物IgM相比,Teleost IgM具有独特的结构组织,这归因于缺乏连接链.
- 在teleost IgM中独特的尾部组件表明了聚合物免疫球蛋白结构的新机制.
- 聚合物免疫球蛋白的结构多样性反映了它们对特定抗体效应因子功能的多样化的进化适应.
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