Mannan-binding lectin serine protease

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Function

Mannan-binding lectin serine protease (MASP) are proteases associated with mannan-binding lectin (MLB). The lectin pathway of complement is part of the innate immunity. The pathway activation occurs via recognition of pathogens by MBL followed by activation of MASP leading to activation of the complement system[1].

Relevance

MASP-1 and MASP-2 contribute to clot formation and may represent an important link between inflammation and thrombosis. MASP levels may be altered in vascular diseases[2].

Structural highlights

. MASP-1, MASP-2 and MASP-3 are 680, 671 and 709 amino acid long respectively. They show a similar domain structure with A chain containing domains CUB1, EGF, CUB2, CCP1, CCP2 followed by a short link region and B chain which is the catalytic domain. The catalytic domain contains the classic serine protease active triad of serine, histidine and aspartic acid[3], [4].


Human MASP-2 chain A sushi 2 domain (grey) and chain B catalytic domain (green) complex with protease inhibitor SGPI-2 (wheat) and sulfate (PDB code 3tvj)

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3D structures of mannan-binding lectin serine protease3D structures of mannan-binding lectin serine protease

Updated on 11-July-2024

ReferencesReferences

  1. Thiel S, Jensen L, Degn SE, Nielsen HJ, Gal P, Dobo J, Jensenius JC. Mannan-binding lectin (MBL)-associated serine protease-1 (MASP-1), a serine protease associated with humoral pattern-recognition molecules: normal and acute-phase levels in serum and stoichiometry of lectin pathway components. Clin Exp Immunol. 2012 Jul;169(1):38-48. doi: 10.1111/j.1365-2249.2012.04584.x. PMID:22670777 doi:http://dx.doi.org/10.1111/j.1365-2249.2012.04584.x
  2. Frauenknecht V, Thiel S, Storm L, Meier N, Arnold M, Schmid JP, Saner H, Schroeder V. Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases. Clin Exp Immunol. 2013 Jul;173(1):112-20. doi: 10.1111/cei.12093. PMID:23607747 doi:http://dx.doi.org/10.1111/cei.12093
  3. Schwaeble W, Dahl MR, Thiel S, Stover C, Jensenius JC. The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes. Immunobiology. 2002 Sep;205(4-5):455-66. PMID:12396007 doi:http://dx.doi.org/10.1078/0171-2985-00146
  4. Heja D, Harmat V, Fodor K, Wilmanns M, Dobo J, Kekesi KA, Zavodszky P, Gal P, Pal G. Monospecific inhibitors show that both mannan-binding lectin-associated serine protease (MASP)-1 and -2 are essential for lectin pathway activation and reveal structural plasticity of MASP-2. J Biol Chem. 2012 Apr 16. PMID:22511776 doi:10.1074/jbc.M112.354332

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Michal Harel, Alexander Berchansky, Joel L. Sussman