ROLE OF THE COLLAGEN-LIKE DOMAIN OF THE HUMAN SERUM MANNAN-BINDING PROTEIN IN THE ACTIVATION OF COMPLEMENT AND THE SECRETION OF THIS LECTIN

Human mannan-binding protein (MBP) is a C-type serum lectin involved in an immunoglobulin-independent host defense. Recently, a common defect of immune opsonin was found to be associated with very low serum levels of MBP. This deficiency was thought to be an effect of a single base substitution in the MBP gene, which resulted in the conversion of Gly54 to Asp. In this study, three mutant MBPs were expressed in COS-1 cells and the effects of these mutations were studied. Gly54Asp-MBP and Gly57Asp-MBP were secreted into the medium almost at the same levels as the wild type MBP, but the formation of higher multimers and the activation of complement were interfered with significantly. The other mutant, in which Leu was inserted into the Gly63- Gln-Gly sequence to restore the collagen motif of the Gly-Xaa-Yaa repeat, was secreted at levels similar to that of the wild type, formed higher multimers and activated complement in a manner not significantly altered from that of the wild type. These results are discussed with regard to the molecular basis of patients with opsonic defects. © 1993 Academic Press, Inc.