Structural superfamilies of the complement system

: The complete primary structures of nearly all the components, regulatory proteins and membrane-associated receptors of the complement system have now been determined by a combination of protein and cDNA sequence analysis. Based on homologies at the amino acid sequence level, three distinct classes of protein domain are evident. They are the C3, C4, C5 family; the serine proteases, and the short consensus repeat family, which is characterized by the widespread occurrence of a novel 60 amino acid repeat structure. A particular feature of the repeat structures in this last family is that they form the structural and functional domains of a range of complement proteins of distinct function, all of which interact with C3b and/or C4b. Detailed analysis of the gene structures of some of these proteins has been carried out. The results have shown that the intron/exon organization of the serine protease domains of factor B and C2 are related to the classical serine proteases at the DNA level. Each short consensus repeat in factor B, C2, C4b-binding protein, murine factor H and also the functionally unrelated interleukin-2 receptor in all except one case is encoded exactly by a single exon, which defines this novel structural unit at the DNA level.