MASPs activation

Stable Identifier
R-GGA-2132206
Type
Reaction [transition]
Species
Gallus gallus
Compartment
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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.

Literature References
PubMed ID Title Journal Year
15814730 Composition of the lectin pathway of complement in Gallus gallus: absence of mannan-binding lectin-associated serine protease-1 in birds

Lynch, NJ, Khan, SU, Stover, CM, Sandrini, SM, Marston, D, Presanis, JS, Schwaeble, WJ

J Immunol 2005
12743029 Crystal structure of the CUB1-EGF-CUB2 region of mannose-binding protein associated serine protease-2

Feinberg, H, Uitdehaag, JC, Davies, JM, Wallis, R, Drickamer, K, Weis, WI

EMBO J 2003
18596036 Crystal structure of the CUB1-EGF-CUB2 domain of human MASP-1/3 and identification of its interaction sites with mannan-binding lectin and ficolins

Teillet, F, Gaboriaud, C, Lacroix, M, Martin, L, Arlaud, GJ, Thielens, NM

J Biol Chem 2008
15034049 Characterization of recombinant mannan-binding lectin-associated serine protease (MASP)-3 suggests an activation mechanism different from that of MASP-1 and MASP-2

Zundel, S, Cseh, S, Lacroix, M, Dahl, MR, Matsushita, M, Andrieu, JP, Schwaeble, WJ, Jensenius, JC, Fujita, T, Arlaud, GJ, Thielens, NM

J Immunol 2004
17204478 Molecular interactions between MASP-2, C4, and C2 and their activation fragments leading to complement activation via the lectin pathway

Wallis, R, Dodds, AW, Mitchell, DA, Sim, RB, Reid, KB, Schwaeble, WJ

J Biol Chem 2007
22691502 Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2

Héja, D, Kocsis, A, Dobó, J, Szilágyi, K, Szász, R, Závodszky, P, Pál, G, Gál, P

Proc. Natl. Acad. Sci. U.S.A. 2012
15060079 Two mechanisms for mannose-binding protein modulation of the activity of its associated serine proteases

Chen, CB, Wallis, R

J Biol Chem 2004
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