Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, 64287 Darmstadt, Germany.
J Mol Biol. 2013 Apr 26;425(8):1302-17. doi: 10.1016/j.jmb.2012.12.017. Epub 2012 Dec 28.
The complement system as a major part of innate immunity is the first line of defense against invading microorganisms. Orchestrated by more than 60 proteins, its major task is to discriminate between host cells and pathogens and to initiate immune response. Additional recognition of necrotic or apoptotic cells demands a fine-tune regulation of this powerful system. C4b-binding protein (C4BP) is the major inhibitor of the classical complement and lectin pathway. The crystal structure of the human C4BP oligomerization domain in its 7α isoform and molecular simulations provide first structural insights of C4BP oligomerization. The heptameric core structure is stabilized by intermolecular disulfide bonds. In addition, thermal shift assays indicate that layers of electrostatic interactions mainly contribute to the extraordinary thermodynamic stability of the complex. These findings make C4BP a promising scaffold for multivalent ligand display with applications in immunology and biological chemistry.
补体系统作为先天免疫系统的主要部分，是抵御入侵微生物的第一道防线。由超过 60 种蛋白质组成的补体系统，其主要任务是区分宿主细胞和病原体，并启动免疫反应。为了精细调控这一强大系统，还需要对坏死或凋亡细胞进行额外识别。C4 结合蛋白（C4BP）是经典补体和凝集素途径的主要抑制剂。人 C4BP 三聚体结构域 7α 异构体的晶体结构和分子模拟为 C4BP 三聚体形成提供了第一个结构见解。七聚体核心结构由分子间二硫键稳定。此外，热转移分析表明，静电相互作用层主要有助于该复合物的非凡热力学稳定性。这些发现使 C4BP 成为在免疫学和生物化学中有应用的多价配体展示的有前途的支架。
