MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway.
Mannan-binding lectin (MBL) activates the complement system through cleavage of C4 and C2. Until recently it was thought that only one serine protease in complex with MBL (MBL-associated serine protease, MASP) mediates complement activation, but with the finding of a second MBL-associated serine protease, MASP-2, the activation process appears more elaborate, possibly resembling that of the C1 complex. The two MASPs share the domain organisation of C1r and C1s and it may be speculated that interaction between the two MASPs is required for complement activation in the same manner as with the C1 proteases. We have demonstrated that MASP-2 is a C4 cleaving component of the MBL/MASP complex. By analogy, one may thus speculate that, upon binding of MBL to carbohydrate, MASP-1 autoactivates and then activates MASP-2, but there is as yet no evidence for this. The components of C1 are present in serum in approximately equimolar amounts, whereas MASP-1 is in large excess over MBL. Pairwise comparison of the four proteases shows the primary structures to be approximately 40% identical. Phylogenetic analysis indicates that MASP-2 is closer to C1r and C1s than is MASP-1, but no particular association between MASP-2 and the C4 cleaving enzyme, C1s, can be deduced from sequence comparison.
Department of Medical Microbiology and Immunology, University of Aarhus, Denmark. vorup@biobase.dk
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Vorup-Jensen
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Jensenius
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Thiel
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002417:Cattle; D037222:Collectins; D003167:Complement Activation; D015923:Complement C1r / Q000737:chemistry; D003173:Complement C1s / Q000737:chemistry; D003175:Complement C2 / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism*; D004789:Enzyme Activation; D019143:Evolution, Molecular; D006801:Humans; D046911:Macromolecular Substances; D050606:Mannose-Binding Protein-Associated Serine Proteases; D010802:Phylogeny; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D013329:Structure-Activity Relationship; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D037222:Collectins; D003175:Complement C2; D003181:Complement C4; D046911:Macromolecular Substances; D050577:Complement C3-C5 Convertases; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D015923:Complement C1r; D003173:Complement C1s