补体系统
先天免疫系统
经典补体途径
细胞生物学
生物
获得性免疫系统
替代补体途径
C3转化酶
蛋白质结构
免疫
功能(生物学)
免疫系统
化学
生物化学
遗传学
作者
B.J.C. Janssen,Eric G. Huizinga,H.C.A. Raaijmakers,Anja Roos,Mohamed R. Daha,Kristina Nilsson‐Ekdahl,Bo Nilsson,Piet Gros
出处
期刊:Nature
[Springer Nature]
日期:2005-09-01
卷期号:437 (7058): 505-511
被引量:479
摘要
The mammalian complement system is a phylogenetically ancient cascade system that has a major role in innate and adaptive immunity. Activation of component C3 (1,641 residues) is central to the three complement pathways and results in inflammation and elimination of self and non-self targets. Here we present crystal structures of native C3 and its final major proteolytic fragment C3c. The structures reveal thirteen domains, nine of which were unpredicted, and suggest that the proteins of the α2-macroglobulin family evolved from a core of eight homologous domains. A double mechanism prevents hydrolysis of the thioester group, essential for covalent attachment of activated C3 to target surfaces. Marked conformational changes in the α-chain, including movement of a critical interaction site through a ring formed by the domains of the β-chain, indicate an unprecedented, conformation-dependent mechanism of activation, regulation and biological function of C3. The complement system is a key component of innate immunity that kills microorganisms directly. It is evolutionarily ancient, predating the immunoglobulins. The crystal structure of the human complement component C3 has now been determined. As well as revealing some of the mechanisms involved in its immune function, the structure has evolutionary implications for mammalian large multi-domain proteins in general — and it may be the largest protein structure (the longest chain and the most domains) so far determined.
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