RESUMEN
At present, the human Factor H protein family represents seven multidomain, multifunctional serum proteins. This group includes the complement and immune regulators Factor H, the Factor H-like protein 1 (FHL-1) and five Factor H-related proteins proteins (FHR-1, -2, -3, -4 and -5). Each is exclusively composed of individually folded protein domains, termed short consensus repeats (SCRs) or complement control modules. Structure-function analyses allowed the localization of the complement regulatory domain of Factor H and FHL-1 in the N-terminal region within SCRs 1-4. In addition, multiple binding sites for C3b, heparin and microbial surface proteins were localized in the N-terminus, within the middle region and also in the C-terminus of Factor H and FHL-1. Recent results show a central role for the C-terminus of Factor H, i.e. SCRs 19-20. These particular domains are conserved in all FHRs identified so far, include contact points for C3b, heparin and microbial surface proteins and represent a 'hot-spot' for gene mutations in patients that suffer from the Factor H-associated form of haemolytic uraemic syndrome.
Asunto(s)
Factor H de Complemento/química , Proteínas del Sistema Complemento/química , Borrelia/patogenicidad , Escherichia coli/patogenicidad , Síndrome Hemolítico-Urémico/genética , Síndrome Hemolítico-Urémico/microbiología , Humanos , Modelos Biológicos , Familia de Multigenes , Mutación , Estructura Terciaria de Proteína , Relación Estructura-ActividadRESUMEN
Factor H is a multidomain and multifunctional protein. As a complement regulator factor H determines the fate of newly formed C3b and controls formation and stability of C3 convertases both in the fluid phase and on cell surfaces. In addition, this plasma protein displays functions outside complement control as it has been suggested to act as an adhesion protein, to be a ligand for the cellular integrin receptor CR3 (CD11b/CD18) and to display chemotactic activity. Genetic and pathophysiological analyses describe a role for factor H in vital body functions. Depletion or the absence of factor H due to genetic reasons leads to unrestricted C3 consumption. A reduced amount of factor H in plasma or mutations within the factor H gene may lead to glomerulonephritis (type II MPGN) or hemolytic uremic syndrome (HUS). Certain pathogenic organisms have been shown to evade complement attack by binding factor H from the host. Such specific factor H binding components have been demonstrated on the surface of microbes, e.g., Streptococcus pyogenes and Neisseria gonorrhoeae. Here, we summarize the current knowledge how abnormalities in function of the central complement regulator factor H are associated with human diseases.
