title: Factor H family proteins: on complement, microbes and human diseases.
abstract: 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.
authors.affiliation: Hans Knoell Institute for Natural Products Research, Beutenbergstrasse 11a, D-07745 Jena, Germany. zipfel@pmail.hki-jena.de
authors.forename: P F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: C
authors.initials: C
authors.lastname: Skerka
authors.forename: J
authors.initials: J
authors.lastname: Hellwage
authors.forename: S T
authors.initials: ST
authors.lastname: Jokiranta
authors.forename: S
authors.initials: S
authors.lastname: Meri
authors.forename: V
authors.initials: V
authors.lastname: Brade
authors.forename: P
authors.initials: P
authors.lastname: Kraiczy
authors.forename: M
authors.initials: M
authors.lastname: Noris
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D001898:Borrelia / Q000472:pathogenicity; D017242:Complement Factor H / Q000737:chemistry*; D003165:Complement System Proteins / Q000737:chemistry*; D004926:Escherichia coli / Q000472:pathogenicity; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000382:microbiology; D006801:Humans; D008954:Models, Biological; D005810:Multigene Family; D009154:Mutation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H; D003165:Complement System Proteins