MASPs activation

Stable Identifier
Reaction [transition]
Gallus gallus
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Cite Us!