Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H.

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Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H. Abstract Text:

C Q Schmidt,A P Herbert,H G Hocking,D ,P N Barlow,C Q Schmidt,A P Herbert,H G Hocking,D ,P N Barlow,C Q Schmidt,A P Herbert,H G Hocking,D Uhrín,P N Barlow,

The 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.

Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H. Publishing Authors By Initials

CQ Schmidt,AP Herbert,HG Hocking,D ,PN Barlow,CQ Schmidt,AP Herbert,HG Hocking,D ,PN Barlow,CQ Schmidt,AP Herbert,HG Hocking,D Uhrín,PN Barlow,

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Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical and experimental immunology

VOLUME: 151

Page Numbers: 14-24

Journal Abbreviation: Clin. Exp. Immunol.

ISSN: 1365-2249

DAY: 17

MONTH: Jan

YEAR: 2008

Translational Mini-Review Series on Complement Factor H: Structural and functional correlations for factor H. Information

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LANGUAGE: eng

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AFFILIATION: The Edinburgh Biomolecular NMR Unit, Schools of Chemistry and Biological Sciences, University of Edinburgh, Edinburgh, UK.

Country: England

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MEDLINETA: Clin Exp Immunol

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