His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form.

Simon J. Clark, Victoria A. Higman, Barbara Mulloy, Stephen J. Perkins, Susan M. Lea, Robert B. Sim, Anthony J. Day*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

135 Citations (Scopus)

Abstract

A polymorphism in complement factor H has recently been associated with age-related macular degeneration (AMD), the leading cause of blindness in the elderly. A histidine rather than a tyrosine at residue position 384 in the mature protein increases the risk of AMD. Here, using a recombinant construct, we show that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and demonstrate that the allotypic variants differentially recognize heparin. This functional alteration may affect binding of factor H to polyanionic patterns on host surfaces, potentially influencing complement activation, immune complex clearance, and inflammation in the macula of AMD patients.

Original languageEnglish
Pages (from-to)24713-24720
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number34
DOIs
Publication statusPublished - 25 Aug 2006

Keywords

  • ESCHERICHIA-COLI
  • SULFATE
  • COMMON
  • BOUND C3B
  • COMPLEMENT FACTOR-H
  • PROTEIN
  • 3-DIMENSIONAL STRUCTURE
  • MEMBRANE
  • IDENTIFICATION
  • POLYMORPHISM

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