MBL and ficolins circulate as complexes with MBL-associated serine proteases (MASPs), which become activated upon lectin binding to the target cell surface. Although three different mammalian MASPs (-1, -2, and -3) were reported to associate with MBL and ficolins, only MASP-2 has a clearly defined role in complement activation [Wallis R et al 2006]. It cleaves C4 and C2 to produce C4a, C4b and C2a,C2b fragments. C2b and C4b form the catalytic component of the C3 convertase (C4b2b). The other two mammalian MASPs (-1 and -3) are alternatively spliced products of a single structural gene. MASP-1 cleaves C2 but not C4 [Chen CB and Wallis R 2004]. MASP-1 may function as MASP-2 activator [Heja D et al 2012]. MASP-3 is not autoactivated. Rather, it is probably activated through the action of an unknown protease [Zundel S et al 2004].
MASPs have a modular structure consisting of an N-terminal CUB domain, a Ca2+-binding EGF-like domain, a second CUB domain, two complement control protein (CCP) modules and a C-terminal serine protease domain. The CUB1-EGF-CUB2 region mediates homodimerization and binding to MBL. The minimal functional unit for complement activation is a MASP homodimer bound to two MBL trimeric subunits [Feinberg H et al 2003; Teille F et al 2008].
Orthologues of human MASP2, MASP3 and MAp19 were identified in the chicken genome [Lynch NJ et al 2005]. MASP1 is considered to be absent in birds. Despite the lack of MASP-1-like enzymatic activity in sera of chicken and other birds, avian lectin pathway complexes efficiently activated C4. The amino-acid sequence of chicken MASP-2 is 54% identical with those of the human and mouse MASP-2, and the organization of the gene is the same as in mammals. Chicken MASP-3 shares approximately 75% of its amino-acid residues with human and Xenopus MASP-3.
