Modular structure of the proteases of the C1r/C1s/MASP family and their role in complement activation.

<p>(<b>A</b>) The generic modular structure of the proteases of this family is shown. MASP-1 and -3, the two proteases coded by the <i>MASP1</i> gene, exhibit a common core (yellow) and unique serine protease (SP) domains. The target of the activation cleavage and the functional domain subdivision are illustrated. The N-terminal interaction domain mediates the binding to the cognate recognition protein and calcium-dependent protease dimerization. In C1r, C1s and MASP-2, the catalytic activity of the C-terminal SP domain is modulated by the preceding CCP1 and CCP2 modules involved in substrate recognition or dimerization <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067962#pone.0067962-BudayovaSpano2" target="_blank">[22]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067962#pone.0067962-Rossi1" target="_blank">[31]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067962#pone.0067962-Kidmose1" target="_blank">[63]</a>. ap: activation peptide. CCP: complement control protein module; CUB: complement C1r/C1s, Uegf, Bmp1 module (<b>B</b>) The activation cascades triggering the lectin and classical complement (C) pathways, and their inhibition by C1-inhibitor, are illustrated. The proteases are associated in large complexes with collagen defence recognition proteins. A possible role for MASP-3 in the activation of the complement alternative pathway needs to be confirmed and its other possible implications outside complement are to be deciphered.