Factor H Family Proteins: On Complement, Microbes and Human Diseases

Biochem Soc Trans. 2002 Nov;30(Pt 6):971-8. doi: 10.1042/bst0300971.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Borrelia / pathogenicity
  • Complement Factor H / chemistry*
  • Complement System Proteins / chemistry*
  • Escherichia coli / pathogenicity
  • Hemolytic-Uremic Syndrome / genetics
  • Hemolytic-Uremic Syndrome / microbiology
  • Humans
  • Models, Biological
  • Multigene Family
  • Mutation
  • Protein Structure, Tertiary
  • Structure-Activity Relationship

Substances

  • complement factor H, human
  • Complement Factor H
  • Complement System Proteins