A common site within factor H SCR 7 responsible for binding heparin, C-reactive protein and streptococcal M protein

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

*Corresponding author for this work

Research output: Contribution to journalReview article

132 Citations (Scopus)


The complement inhibitor factor H (fH) interacts via its seventh short consensus repeat (SCR) domain with multiple ligands including heparin, streptococcal M protein and C-reactive protein (CRP). The aim of this study was to localize the residues in SCR 7 required for these interactions. We initially built a homology model of fH SCR 6-7 using the averaged NMR structures of fH SCR 15-16 and vaccinia control protein SCR 3-4 as templates. Electrostatic potentials of the model's surface demonstrated a co-localization of three clusters of positively charged residues on SCR 7, labeled site A (R369 and K370), site B (R386 and K387) and site C (K392). These residues, localized to the linker region preceding SCR 7 and to the end of a "hypervariable loop" in SCR 7, were systematically replaced with uncharged alanine residues in an fH construct containing SCR 1-7. The resulting proteins were expressed in the methylotrophic yeast, Pichia pastoris. By ELISA analysis we demonstrated: first, that substituting site A inhibited heparin and CRP binding; secondly, that substituting site B inhibited binding to heparin, CRP and M protein; and thirdly, that substituting site C clearly inhibited only heparin binding.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalEuropean Journal of Immunology
Issue number4
Publication statusPublished - 1 Apr 2003
Externally publishedYes



  • Alternative pathway
  • Complement
  • Streptococcus

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