Mannose-Associated Serine Protease 1 (MASP-1)

The complement lectin pathway plays an important role in the clearance of pathogenic microbes. Its activation is mediated by the binding of recognition molecules to glycosylated structures on the surface of a variety of microorganisms, which cannot be achieved without the participation of mannose-associated serine proteases (MASP).

3 MASPs have been identified currently, MASP-1, MASP-2, and MASP-3. MASP-1, also known as mannan-binding lectin serine protease 1, is synthesized as a zymogen with a single-chain polypeptide of 699 residues. The structure of MASP-1 is analogous to C1r and C1s, consisting of 6 domains: a serine protease domain, two complement control proteins (CCPs), and an epidermal growth factor (EGF)-like domain locating in the middle of two CUB (C1r/C1s, urchin-EGF, and bone morphogenetic protein-1) domains. The N-terminal CUB domain and EGF domain are antiparallel, forming a mature MASP homodimer in a Ca²⁺-dependent manner. The two CUB domains are responsible for binding to the collagen-like domains of recognition molecules, and the serine protease domain has a substrate-binding groove allowing cleavage substrates.

Normally, the recognition molecules are complexed with MASPs. Once recognition molecules bind to pathogen carbohydrate, MASP-1 will undergo a conformation change to be activated by cleavage between the second CCP and serine protease domain. The cleavage generates two active polypeptides, A-chain and B-chain, linked by a disulfide bond. The active MASP-1 then activates MASP-2, which subsequently cleaves complement C2 and C4, leading to the C3 convertase formation and complement activation. Additionally, MASP-1 also is capable of cleaving coagulation factors, such as fibrinogen and factor XIII, involving in coagulation.

Fig.1 MASP molecules in the activation of the lectin pathway. (Boldt, 2016)

Reference

1. Boldt A.B.W.; et al. MASP1 and MASP2. In: Choi S. (eds) Encyclopedia of Signaling Molecules. 2016.