Structure and function of mannan-binding proteins isolated from human liver and serum

Abstract

Mannan-binding proteins (MBPs) occur in two forms, both of which are synthesized in the liver. Although two different MBP cDNAs have been cloned and characterized for rat and mouse, only one form of human MBP cDNA has been isolated. In this study, two forms of human MBP, liver MBP (L-MBP) and serum MBP (S-MBP), were purified from liver and serum and characterized, respectively. The amino acid sequences of these two human MBPs were identical and consistent with those deduced from the cDNA sequence. The most significant difference between L-MBP and S-MBP was the number of subunits, which was about 9 in L-MBP and 18 in S-MBP. Furthermore, S-MBP but not L-MBP had the ability to activate the complement. These results suggested that a newly synthesized protein is processed post-translationally into two forms, S-MBP and L-MBP, in human liver. Recombinant MBP synthesized in COS-1 cells, after transfection with human MBP cDNA, was secreted into the medium, suggesting that COS-1 cells lack a mechanism for differentiating S-MBP and L-MBP. A mutant MBP synthesized in COS-1 cells which lacked a sequence comprising 9 amino acid residues at the beginning of the collagen-like domain had no ability to activate the complement, suggesting that this sequence plays an important role in the activation of the complement by human MBP.