title: Carbohydrate recognition and complement activation by rat ficolin-B.
abstract: Ficolins are innate immune components that bind to PAMPs and structures on apoptotic cells. Humans produce two serum forms (L- and H-ficolin) and a leukocyte-associated form (M-ficolin), whereas rodents and most other mammals produce ficolins-A and -B, orthologues of L- and M-ficolin, respectively. All three human ficolins, together with mouse and rat ficolin-A, associate with mannan-binding lectin-associated serine proteases (MASPs) and activate the lectin pathway of complement on PAMPs. By contrast, mouse ficolin-B does not bind MASPs and cannot activate complement. Because of these striking differences together with the lack of functional information for other ficolin-B orthologues, we have characterized rat ficolin-B, and compared its physical and biochemical properties with its serum counterpart. The data show that both rat ficolins have archetypal structures consisting of oligomers of a trimeric subunit. Ficolin-B recognized mainly sialyated sugars, characteristic of exogenous and endogenous ligands, whereas ficolin-A had a surprisingly narrow specificity, binding strongly to only one of 320 structures tested: an N-acetylated trisaccharide. Surprisingly, rat ficolin-B activated MASP-2 comparable to ficolin-A. Mutagenesis data reveal that lack of activity in mouse ficolin-B is probably caused by a single amino acid change in the putative MASP-binding site that blocks the ficolin-MASP interaction.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
authors.forename: Umakhanth Venkatraman
authors.initials: UV
authors.lastname: Girija
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mitchell
authors.forename: Silke
authors.initials: S
authors.lastname: Roscher
authors.forename: Russell
authors.initials: R
authors.lastname: Wallis
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D000097604:Ficolins
chemical_list: D002241:Carbohydrates; D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins