MASP1 (MBL-associated serine protease 1)

Area of Science:

• Immunology
• Biochemistry
• Molecular Biology

Background:

• Mannose-binding lectin (MBL) is a crucial component of the innate immune system.
• MBL activates complement through a unique pathway involving MBL-associated serine proteases (MASPs).
• MASPs, specifically MASP1 and MASP2, are structurally related to C1r and C1s, forming a novel serine protease family.

Purpose of the Study:

• To investigate the structural and functional classification of the MASP/C1r/C1s serine protease family.
• To elucidate the evolutionary relationship and potential ancestral roles of MASP proteases.

Main Methods:

• Comparative analysis of MASP cDNA sequences from various vertebrates and ascidians.
• Identification of conserved structural features within the serine protease domains, including histidine loops and active-serine encoding.

Main Results:

• Two distinct groups within the MASP/C1r/C1s family were identified based on sequence analysis.
• Group 1 (e.g., human MASP1) is characterized by a histidine loop and TCN-encoded active serine, suggesting a role in C3 activation.
• Group 2 (e.g., human MASP2, C1r, C1s) possesses different structural features, including an AGY-encoded active serine.

Conclusions:

• The MASP/C1r/C1s family exhibits significant structural divergence, leading to two distinct functional groups.
• The TCN-type MASP, exemplified by MASP1, likely represents an ancestral protease that predates the AGY-type and was pivotal in C3 cleavage.
• MASP2 is likely involved in C4 cleavage, though further functional validation is necessary.