Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins.
Mannan-binding lectin (MBL), L-ficolin, M-ficolin and H-ficolin are all complement activating soluble pattern recognition molecules with recognition domains linked to collagen-like regions. All four may form complexes with four structurally related proteins, the three MBL-associated serine proteases (MASPs), MASP-1, MASP-2 and MASP-3, and a smaller MBL-associated protein (MAp19). The four recognition molecules recognize patterns of carbohydrate or acetyl-group containing ligands. After binding to the relevant targets all four are able to activate the complement system. We thus have a system where four different and/or overlapping patterns of microbial origin or patterns of altered-self may be recognized, but in all cases the signalling molecules, the MASPs, are shared. MASP-1 and MASP-3 are formed from one gene, MASP1/3, by alternative splicing generating two different mRNAs from a single primary transcript. Similarly MASP-2 and MAp19 are both generated from one gene, MASP-2/MAp19, by alternative splicing. A number of non-synonymous polymorphisms of the four recognition molecules and of the MASPs are known, and the implications of these alterations are being studied. The clinical impact of deficiencies will be discussed.
Thiel
Steffen
S
Department of Medical Microbiology and Immunology, University of Aarhus, Wilhelms Meyers Allé, 8000 Aarhus C, Denmark. st@microbiology.au.dk
D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000737:chemistry*; D003167:Complement Activation / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D012995:Solubility; D000097604:Ficolins
D003094:Collagen; D037102:Lectins; D037601:Mannose-Binding Lectin; D051192:Receptors, Pattern Recognition; D000097604:Ficolins