کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832656 1163841 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Native, amyloid fibrils and β-oligomers of the C-terminal domain of human prion protein display differential activation of complement and bind C1q, factor H and C4b-binding protein directly
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Native, amyloid fibrils and β-oligomers of the C-terminal domain of human prion protein display differential activation of complement and bind C1q, factor H and C4b-binding protein directly
چکیده انگلیسی

Prion protein (PrP) is an endogenous protein involved in the pathogenesis of bovine spongiform encephalopathy and Creutzfeldt–Jakob disease. Murine PrP has been reported to bind C1q and activate the classical pathway of complement in a copper-dependent manner. Here we show that various conformational isoforms (native, amyloid fibrils, and β-oligomers) of recombinant human PrP (90–231 and 121–231) bind C1q and activate complement. PrP binds both the globular head and collagenous stalk domains of C1q. Native, β-oligomeric and amyloid fibrils of PrP all activate the classical and alternative pathways of complement to different extent. However, they do not trigger the lectin pathway. Of the tested PrP conformational isoforms we find that β-oligomers bind C1q and activate complement most strongly. Membrane attack complex formation initiated by PrP is subdued in comparison to deposition of early complement components. This is most likely attributed to the interaction between human PrP and complement inhibitors factor H and C4b-binding protein. Accordingly, PrP-triggered complement activation in the terminal pathway was increased in serum lacking C4b-binding protein. Taken together the present study indicates that complement activation may be an important factor in human prion diseases, suggesting that complement induced activities may prove relevant therapeutic targets.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 45, Issue 11, June 2008, Pages 3213–3221
نویسندگان
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