MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation.
Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(2+)-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (K(D) = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
Degn
Søren E
SE
Departments of Medical Microbiology and Immunology, University of Aarhus, Arhus, Denmark.
Hansen
Annette G
AG
Steffensen
Rudi
R
Jacobsen
Christian
C
Jensenius
Jens C
JC
Thiel
Steffen
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003167:Complement Activation; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020349:Surface Plasmon Resonance; D000097604:Ficolins
D007527:Isoenzymes; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012333:RNA, Messenger; D000097604:Ficolins; C084067:MASP1 protein, human