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

Jin Wu, You-qiang Wu, Daniel Ricklin, Bert J C Janssen, John D Lambris, Piet Gros

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)728-733
JournalNature Immunology
Volume10
Issue number7
DOIs
Publication statusPublished - 1 Jul 2009

Fingerprint

Dive into the research topics of 'Structure of complement fragment C3b–factor H and implications for host protection by complement regulators'. Together they form a unique fingerprint.

Cite this