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Nat Immunol. 2009 Jul;10(7):728-33. doi: 10.1038/ni.1755. Epub 2009 Jun 7.

Structure of complement fragment C3b-factor H and implications for host protection by complement regulators.

Author information

  • 1Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Utrecht, The Netherlands.

Abstract

Factor H (FH) is an abundant regulator of complement activation and protects host cells from self-attack by complement. Here we provide insight into the regulatory activity of FH by solving the crystal structure of the first four domains of FH in complex with its target, complement fragment C3b. FH interacted with multiple domains of C3b, covering a large, extended surface area. The structure indicated that FH destabilizes the C3 convertase by competition and electrostatic repulsion and that FH enables proteolytic degradation of C3b by providing a binding platform for protease factor I while stabilizing the overall domain arrangement of C3b. Our results offer general models for complement regulation and provide structural explanations for disease-related mutations in the genes encoding both FH and C3b.

PMID:
19503104
[PubMed - indexed for MEDLINE]
PMCID:
PMC2713992
Free PMC Article

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