Native, amyloid fibrils and beta-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.
Holmér, Andreas LU ; Nyström, Sofie ; Hammarström, Per and Blom, Anna LU
(2008)
In Molecular Immunology
45.
p.3213-3221
- Abstract
- 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 beta-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, beta-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... (More)
- 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 beta-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, beta-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 beta-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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1147434
- author
- Holmér, Andreas
LU
; Nyström, Sofie
; Hammarström, Per
and Blom, Anna
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Immunology
- volume
- 45
- pages
- 3213 - 3221
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- wos:000257024800023
- pmid:18406463
- scopus:43449086676
- ISSN
- 1872-9142
- DOI
- 10.1016/j.molimm.2008.02.023
- language
- English
- LU publication?
- yes
- id
- baf8eb36-8acd-4c82-891a-24501f12b864 (old id 1147434)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18406463?dopt=Abstract
- date added to LUP
- 2016-04-04 09:37:58
- date last changed
- 2022-01-29 18:48:46
@article{baf8eb36-8acd-4c82-891a-24501f12b864,
abstract = {{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 beta-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, beta-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 beta-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.}},
author = {{Holmér, Andreas and Nyström, Sofie and Hammarström, Per and Blom, Anna}},
issn = {{1872-9142}},
language = {{eng}},
pages = {{3213--3221}},
publisher = {{Pergamon Press Ltd.}},
series = {{Molecular Immunology}},
title = {{Native, amyloid fibrils and beta-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.}},
url = {{http://dx.doi.org/10.1016/j.molimm.2008.02.023}},
doi = {{10.1016/j.molimm.2008.02.023}},
volume = {{45}},
year = {{2008}},
}