Evolution of the initiating enzymes of the complement system.docVIP

/2001/3/1/reviews/1001.1 Minireview Evolution of the initiating enzymes of the complement system Masaru Nonaka and Seita Miyazawa Address: Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo, Tokyo 113-0033, Japan. Correspondence: Masaru Nonaka. E-mail: mnonaka@biol.s.u-tokyo.ac.jp Published: 14 December 2001 GenomeBiology 2001, 3(1):reviews1001.1–1001.5 The electronic version of this article is the complete one and can be found online at /2001/3/1/reviews/1001 ? BioMed Central Ltd (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract Analysis of the human MASP-1/3 gene, which encodes two proteases of the lectin-triggered complement cascade, has revealed alternatively used serine-protease-encoding regions for the gene’s two protein products. Phylogenetic studies indicate that one arose by retrotransposition early in vertebrate evolution, supporting the idea that the lectin branch of the complement cascade arose earlier than the ‘classical’ pathway. The mammalian complement system, as one of the major constituents of innate immunity, plays a pivotal role in defending the body against pathogenic microorganisms. It has more than 30 components, organized into three major pathways: the ?classical? pathway, triggered by antibodies; the ?lectin? pathway, triggered by engagement of mannan- binding protein; and the ?alternative? pathway, triggered directly by pathogens (see Table 1). Of the 30 complement components, about one-fourth are serine proteases that are important for the activation or regulation of the whole system. Among these, C1r and C1s of the classical pathway and the MASPs (mannan-binding-protein-associated serine proteases) of the lectin pathway are crucial for starting the proteolytic activation cascades of their respective pathways. These components constitute a serine-protease family of the chymotrypsin type b