Two Mechanisms for Mannose-binding Protein Modulation of the Activity of Its Associated Serine Proteases

Serum mannose-binding protein (MBP) neutralizes invading microorganisms by binding to cell surface carbohydrates and activating MBP-associated serine proteases-1, -2, and -3 (MASPs). MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. To analyze the mechanisms of activation and substrate recognition by MASP-2, zymogen and activated forms have been produced, and MBP·MASP-2 complexes have been created. These preparations have been used to show that MBP modulates MASP-2 activity in two ways. First, MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP·MASP-2 complexes bind to MBP MASP-2 activation MASP-2 to C4 to activated MASP-2 to that substrate the and cleaves C2 MASP-2 complement activation by MBP·MASP-2 activation Serum mannose-binding protein (MBP) neutralizes invading microorganisms by binding to cell surface carbohydrates and activating MBP-associated serine proteases-1, -2, and -3 (MASPs). MASP-2 subsequently cleaves complement components C2 and C4 to activate the complement cascade. To analyze the mechanisms of activation and substrate recognition by MASP-2, zymogen and activated forms have been produced, and MBP·MASP-2 complexes have been created. These preparations have been used to show that MBP modulates MASP-2 activity in two ways. First, MBP stimulates MASP-2 autoactivation by increasing the rate of autocatalysis when MBP·MASP-2 complexes bind to MBP MASP-2 activation MASP-2 to C4 to activated MASP-2 to that substrate the and cleaves C2 MASP-2 complement activation by MBP·MASP-2 activation Serum mannose-binding protein used mannose-binding complement in complement and MBP-associated serine used mannose-binding complement in complement and MBP-associated serine the recognition of the of the complement invading microorganisms by binding to cell surface and and activating MBP-associated serine -2, and of and of the of complement activation of two by and MBP binding to the by two and of the the of the serine MASP-2 in complement cleaves the and in the forms to the C2 to and by to the and forms the of the of the and the cell in the cell MASP-2 cleaves C4 C2 activation to to the mechanisms that activation in the the activity by binding to and the the have of been to complement components C2 and in that of of that recognition recognition to by of bind the of in the the to two MBP that MBP bind MBP and bind to two the MASP-2 activation been by the of zymogen and activated forms of MASP-2 and in show that MBP modulates the activity of MASP-2 and and and protein and by in protein by and of of MASP-2 and MASP-2, in the serine to by in and of MASP-2, by the the zymogen activation and the activated by protein in and to of of the MASP-2 by of by the zymogen the recognition of the serine and forms of activated by in and to by the of C2 and C4 complement C2 the the and the of the of to the of the of the of the C4 by of and by the by and of C2 and C4 the C2 and C4 to the of the by and the by of the of the that the by in the cell and that been of MBP C2 by of of that of and of of and of protein in in C2 by To C2 by the in rate of protein of by in the protein that the of and of C4 the by in rate of of and C4 by of used to that the by in to of by MASP-2 and activated MASP-2 in and in in that the of in the by 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