Title : Interaction properties of human
mannan-binding lectin (
MBL )-associated
serine proteases-1 and
-2, MBL-associated protein 19 , and
MBL
Abstract :
- The mannan-binding lectin ( MBL ) activation pathway of complement plays an important role in the innate immune defense against pathogenic microorganisms
- In human serum, two MBL-associated serine proteases ( MASP-1 , MASP-2 ) and MBL-associated protein 19 ( MAp19 ) were found to be associated with MBL
- With a view to investigate the interaction properties of these proteins , human MASP-1 , MASP-2 , MAp19 , as well as the N-terminal complement subcomponents C1r/C1s , Uegf, and bone morphogenetic protein-1-epidermal growth factor (CUB- EGF ) segments of MASP-1 and MASP-2 , were expressed in insect or human kidney cells, and MBL was isolated from human serum
- Sedimentation velocity analysis indicated that the MASP-1 and MASP-2 CUB- EGF segments and the homologous protein MAp19 all behaved as homodimers (2.8-3.2 S) in the presence of Ca(2 +)
- Although the latter two dimers were not dissociated by EDTA, their physical properties were affected
- In contrast, the MASP-1 CUB- EGF homodimer was not sensitive to EDTA
- The three proteins and full-length MASP-1 and MASP-2 showed no interaction with each other as judged by gel filtration and surface plasmon resonance spectroscopy
- Using the latter technique, MASP-1 , MASP-2 , their CUB- EGF segments, and MAp19 were each shown to bind to immobilized MBL , with K:(D) values of 0.8 nM ( MASP-2 ), 1.4 nM ( MASP-1 ), 13.0 nM ( MAp19 and MASP-2 CUB- EGF ), and 25.7 nM ( MASP-1 CUB- EGF )
- The binding was Ca(2 +)-dependent and fully sensitive to EDTA in all cases
- These data indicate that MASP-1 , MASP-2 , and MAp19 each associate as homodimers , and individually form Ca(2 +)-dependent complexes with MBL through the CUB- EGF pair of each protein
- This suggests that distinct MBL /MASP complexes may be involved in the activation or regulation of the MBL pathway
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):