Multiple ligand binding sites on domain seven of human complement factor H

Eleni Giannakis, Dean A. Male, Rebecca J. Ormsby, Carolyn Mold, T. Sakari Jokiranta, Shoba Ranganathan, David L. Gordon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Foreign particles and damaged host cells can activate the complement system leading to their destruction by the host defense system. Factor H (fH) plays a vital role in restricting complement activation on host cells through interactions with polyanions such as heparin, while allowing activation to proceed on foreign surfaces. Complement activation by damaged host cells is also down regulated by fH, which is localized to injured areas through interactions with C-reactive protein (CRP). A number of pathogens have developed mechanisms by which they can also bind fH and thus exploit its protective properties. One such organism is Group A Streptococcus (GAS) which mediates fH binding via its surface expressed M-protein. fH consists of 20 conserved short consensus repeat (SCR) units and mutagenesis studies indicate that the seventh repeat is responsible for interactions with heparin, CRP and M-protein. We recently performed molecular modelling of fH SCR 7 and identified a cluster of positively charged residues on one face of the domain. By alanine replacement mutagenesis, we demonstrated that these residues are involved in heparin, CRP and M protein binding, which indicates that there is a common site within fH SCR 7 responsible for multiple ligand recognition.

Original languageEnglish
Pages (from-to)433-443
Number of pages11
JournalInternational Immunopharmacology
Volume1
Issue number3
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • C-reactive protein
  • Complement
  • Factor H
  • Heparin
  • Streptococcal M-protein

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