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Carbohydrate recognition and complement activation by rat ficolin-B
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Girija, Umakhanth Venkatraman, Mitchell, Daniel A., Roscher, Silke and Wallis, Russell (2011) Carbohydrate recognition and complement activation by rat ficolin-B. European Journal of Immunology, Volume 41 (Number 1). pp. 214-223. doi:10.1002/eji.201040612 ISSN 0014-2980.
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Official URL: http://dx.doi.org/10.1002/eji.201040612
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.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > R Medicine (General) | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Library of Congress Subject Headings (LCSH): | Lectins, Immunity | ||||
Journal or Publication Title: | European Journal of Immunology | ||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
ISSN: | 0014-2980 | ||||
Official Date: | January 2011 | ||||
Dates: |
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Volume: | Volume 41 | ||||
Number: | Number 1 | ||||
Page Range: | pp. 214-223 | ||||
DOI: | 10.1002/eji.201040612 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 19 December 2015 | ||||
Date of first compliant Open Access: | 19 December 2015 | ||||
Funder: | Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), National Institute of General Medical Sciences (U.S.) (NIGMS) | ||||
Grant number: | G0501425 (MRC), 077400 (WT), GM62116 (NIGMS) |
Data sourced from Thomson Reuters' Web of Knowledge
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