The Croonian Lecture, 1980 - The complex proteases of the complement system

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Abstract
The assembly and activation of the early components of complement, after their interaction with antibody–antigen complexes, are described in terms of the structures of the different proteins taking part. C1q, a molecule of unique half collagen-half globular structure, binds to the second constant domain of the antibody molecules through its six globular heads. A tetrameric complex of C1r2–C1s2binds to the collagenous tails and leads to formation of the serine-type proteases C1¯r and C1¯s. C1¯s activates C4, which forms a covalent bond between its α' chain and the Fab section of the antibody. C2 is also activated by C1¯s and associates with the bound C4¯molecule to form C42¯, a labile protease that activates C3, but which loses activity as the C2¯peptide chains dissociate from C4¯. C2, by analogy with factor B, the equivalent component of the alternative pathway of activation, appears to be a novel type of serine protease with a similar catalytic site but different activation mechanism to the serine proteases that have been described previously.