title: His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form.
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.
authors.affiliation: Medical Research Council (MRC) Immunochemistry Unit and Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Clark
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Higman
authors.forename: Barbara
authors.initials: B
authors.lastname: Mulloy
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lea
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001665:Binding Sites / Q000235:genetics; D003167:Complement Activation; D017242:Complement Factor H / Q000235:genetics* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006639:Histidine; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011994:Recombinant Proteins; D006639:Histidine; D017242:Complement Factor H; D006493:Heparin