The phylogeny and evolution of the thioester bond-containing proteins C3, C4 and alpha 2-macroglobulin

The complement system is an effector of both the acquired and innate immune systems of the higher vertebrates. It has been traced back at least as far as the echinoderms and so predates the appearance of the antibodies, T-cell receptors and MHC molecules of adaptive immunity. Central to the function of complement is the reaction of the thioester bond located within the structure of complement components C3 and C4. The structural thioester first appeared in a protease inhibitor, alpha 2-macroglobulin, in which it is involved in the immobilisation and entrapment of proteases. An important development in the C3 molecule has been the acquisition of a catalytic His residue which greatly increases the rate of reaction of the thioester with hydroxyl groups and with water.