1. Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H
- Author
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Dušan Uhrín, Andrew P. Herbert, Paul N. Barlow, Christoph Q. Schmidt, and Henry G. Hocking
- Subjects
Models, Molecular ,musculoskeletal diseases ,Protein Conformation ,Molecular Sequence Data ,Immunology ,Translational Mini-Review Series: Complement Factor H ,Context (language use) ,C5-convertase ,Structure-Activity Relationship ,atypical haemolytic uraemic syndrome ,Humans ,Immunology and Allergy ,complement ,Amino Acid Sequence ,Binding site ,age-related macular degeneration ,chemistry.chemical_classification ,Binding Sites ,biology ,Chemistry ,Complement C3 ,NMR ,Complement system ,glycosaminoglycans ,Complement Factor H ,Factor H ,Mutation ,Alternative complement pathway ,biology.protein ,Glycoprotein ,Sequence Alignment ,Complement control protein - Abstract
SummaryOTHER ARTICLES PUBLISHED IN THIS TRANSLATIONAL MINI-REVIEW SERIES ON COMPLEMENT FACTOR HGenetics and disease associations of human complement factor H. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03552.xTherapies of renal diseases associated with complement factor H abnormalities: atypical haemolytic uraemic syndrome and membranoproliferative glomerulonephritis. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03558.xRenal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol 2008; 151: doi:10.1111/j.1365-2249.2007.03574.xThe 155-kDa glycoprotein, complement factor H (CFH), is a regulator of complement activation that is abundant in human plasma. Three-dimensional structures of over half the 20 complement control protein (CCP) modules in CFH have been solved in the context of single-, double- and triple-module segments. Proven binding sites for C3b occupy the N and C termini of this elongated molecule and may be brought together by a bend in CFH mediated by its central CCP modules. The C-terminal CCP 20 is key to the ability of the molecule to adhere to polyanionic markers on self-surfaces where CFH acts to regulate amplification of the alternative pathway of complement. The surface patch on CCP 20 that binds to model glycosaminoglycans has been mapped using nuclear magnetic resonance (NMR), as has a second glycosaminoglycan-binding patch on CCP 7. These patches include many of the residue positions at which sequence variations have been linked to three complement-mediated disorders: dense deposit disease, age-related macular degeneration and atypical haemolytic uraemic syndrome. In one plausible model, CCP 20 anchors CFH to self-surfaces via a C3b/polyanion composite binding site, CCP 7 acts as a ‘proof-reader’ to help discriminate self- from non-self patterns of sulphation, and CCPs 1–4 disrupt C3/C5 convertase formation and stability.
- Published
- 2007