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Molecular characterization of a novel serine protease involved in activation of the complement system by
1Department of Biochemistry, Fukushima Medical College, Japan.
Abstract:
Mannose-binding protein (MBP) plays an important role in host defense by recognizing sugar residues on certain pathogens and activating the complement cascade. Recently, we described a new protease, designated MBP-associated serine protease (MASP) which is required for complement activation by MBP. We have cloned the cDNA that encodes this protease and found that the deduced amino acid sequence contains an epidermal growth factor-like domain, two short consensus repeats and a serine protease domain. The overall structure of MASP is similar to serine proteases of the first complement component complex, C1r-C1s. Unlike C1r-C1s, however, MASP has a histidine loop structure common to many serine proteases such as trypsin and chymotrypsin. The MASP gene was mapped on the long arm of chromosome 3 which is different from C1r-C1s as well as from trypsin and chymotrypsin. These findings suggest that MASP may have emerged prior to C1r-C1s from a common ancestor. This implies that MBP-MASP, a complex of lectin and serine protease, presumably evolved prior to adaptive immune recognition involving antibody and the classical complement pathway.
Insights
Mannose-binding protein-associated serine protease (MASP) is essential for host defense. Its structure suggests it evolved before the classical complement pathway, offering insights into early immune system development.
Area of Science:
- Immunology
- Biochemistry
- Genetics
Background:
- Mannose-binding protein (MBP) is crucial for innate immunity, recognizing pathogens and activating the complement system.
- MBP-associated serine protease (MASP) was recently identified as essential for MBP-mediated complement activation.
Purpose of the Study:
- To clone the cDNA encoding MASP.
- To analyze the structural and evolutionary relationship of MASP to other serine proteases.
Main Methods:
- cDNA cloning of MASP.
- Deduced amino acid sequence analysis.
- Gene mapping of MASP.
Main Results:
- MASP cDNA was cloned, revealing domains similar to complement proteases C1r-C1s.
- MASP possesses a unique histidine loop structure found in other serine proteases.
- The MASP gene was mapped to chromosome 3, distinct from C1r-C1s and trypsin/chymotrypsin.
Conclusions:
- MASP shares structural similarities with C1r-C1s, suggesting a common ancestor.
- MASP likely predates C1r-C1s and the antibody-dependent classical complement pathway.
- The MBP-MASP complex represents an early form of immune recognition evolved before adaptive immunity.