MASP-2, THE C3 CONVERTASE GENERATING PROTEASE OF THE MBLECTIN COMPLEMENT ACTIVATING PATHWAY

Mannan-binding lectin (MBL) activates the complement system through cl eavage of C4 and C2. Until recently it was thought that only one serin e protease in complex with MBL (MBL-associated serine protease, MASP) mediates complement activation, but with the finding of a second MEL-a ssociated 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 acti vation in the same manner as with the C1 proteases. We have demonstrat ed 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 carbohydr ate, MASP-1 autoactivates and then activates MASP-2, but there is as y et no evidence for this. The components of C1 are present in serum in approximately equimolar amounts, whereas MASP-1 is in large excess ove r MEL. Pairwise comparison of the four proteases shows the primary str uctures to be approximately 40% identical. Phylogenetic analysis indic ates that MASP-2 is closer to C1r and C1s than is MASP-1, but no parti cular association between MASP-2 and the C4 cleaving enzyme, C1s, can be deduced from sequence comparison.