Human factor H-related protein 2 (CFHR2) regulates complement activation.

Eberhardt HU, Buhlmann D, Hortschansky P, Chen Q, Böhm S, Kemper MJ, Wallich R, Hartmann A, Hallström T, Zipfel PF, Skerka C (2013) Human factor H-related protein 2 (CFHR2) regulates complement activation. PLoS One 8(11), e78617. PubMed

ILRS Authors

Peter F. Zipfel Christine Skerka Denise Buhlmann Qian Chen Hannes Eberhardt

Projects

The role of CFHR proteins in human autoimmune diseases
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Functional characterization of the soluble complement receptor type II (CR2/CD21) in infection
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Abstract

Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs). Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

Identifier

doi: 10.1371/journal.pone.0078617 PMID: 24260121

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