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MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway
T Vorup-Jensen1, J C Jensenius, S Thiel
1Department of Medical Microbiology and Immunology, University of Aarhus, Denmark. vorup@biobase.dk
Immunobiology
|October 20, 1998
Summary
Mannan-binding lectin (MBL) and its associated proteases (MASPs) activate the complement system. MASP-2 is confirmed as the C4 cleaving component, suggesting a more complex activation pathway.
Area of Science:
- Immunology
- Biochemistry
- Molecular Biology
Background:
- Mannan-binding lectin (MBL) initiates complement activation via C4 and C2 cleavage.
- Previously, only one MBL-associated serine protease (MASP) was known; MASP-2 has since been identified.
- The MBL/MASP complex's activation mechanism may resemble the C1 complex.
Purpose of the Study:
- To investigate the role of MASP-2 in MBL-mediated complement activation.
- To elucidate the functional relationship between MASP-1 and MASP-2.
- To compare the structural and phylogenetic relationships of MASPs with C1 proteases.
Main Methods:
- Demonstration of MASP-2 as the C4 cleaving component within the MBL/MASP complex.
- Analysis of domain organization and sequence identity between MASPs and C1 proteases.
- Phylogenetic analysis to infer evolutionary relationships.
Main Results:
- MASP-2 was confirmed as the C4 cleaving component of the MBL/MASP complex.
- MASP-1 is present in significant excess over MBL in serum.
- Phylogenetic analysis suggests MASP-2 is more closely related to C1r and C1s than MASP-1.
Conclusions:
- MASP-2 plays a direct role in cleaving C4, a key step in complement activation.
- The MBL/MASP system's activation may involve intricate interactions between MASP-1 and MASP-2.
- While MASP-2 shares similarities with C1s, direct functional associations require further investigation.