Factor H family proteins: on complement, microbes and human diseases. (November 2002)

• Record Type: Journal Article
• Authors: Zipfel, P. F.; Skerka, C.; Hellwage, J.; Jokiranta, S. T.; Meri, S.; Brade, V.; Kraiczy, P.; Noris, M.; Remuzzi, G.
• Is Part Of: Biochemical Society transactions. Volume 30:Number 6(2002)
• Page Start: 971
• Page End: 978
• Publication Date: 2002-11
• Subjects: complement regulation -- Factor H protein family -- haemolytic uraemic syndrome -- immunevasion -- innate immunity -- microbial evasion strategy; CRASP, complement regulatory-acquiring surface protein -- FHL-1, Factor H-like protein -- FHR, Factor H-related protein -- HUS, haemolytic uraemic syndrome -- RCA, regulator of complement activation -- SCR, short consensus repeat; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0300971
• Languages: English
• ISSNs: 0300-5127

Abstract

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.