Carbohydrate recognition and complement activation by rat ficolin-B
Girija, Umakhanth Venkatraman, Mitchell, Daniel Anthony, Roscher, Silke and Wallis, Russell. (2011) Carbohydrate recognition and complement activation by rat ficolin-B. European Journal of Immunology, Vol.41 (No.1). pp. 214-223. ISSN 0014-2980Full text not available from this repository.
Official URL: http://dx.doi.org/10.1002/eji.201040612
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.
|Item Type:||Journal Article|
|Subjects:||R Medicine > R Medicine (General)|
|Divisions:||Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||European Journal of Immunology|
|Publisher:||Wiley - V C H Verlag GmbH & Co. KGaA|
|Page Range:||pp. 214-223|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Medical Research Council (Great Britain) (MRC), Wellcome Trust , National Institute of General Medical Sciences (NIGMS)|
|Grant number:||G0501425 (MRC), 077400 (Wellcome Trust), GM62116 (NIGMS)|
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