Biochemical Analysis of a Common Human Polymorphism Associated with Age-Related Macular Degeneration

• DOI: 10.1021/bi700459a
• Publication Date: 2007-06-20T13:00:35Z
• Authors: Jiamei Yu; Patrick Wiita; Riki Kawaguchi; Jane Honda; Adam Jorgensen; Kang Zhang; Vincent A. Fischetti; Hui Sun
• Keywords: Streptococcus Pyogenes

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. A large number human genetic studies have associated a common variant (Y402H) complement factor H (CFH) with highly significant increase AMD risk. CFH modular protein 20 homologous short consensus repeats (SCRs). The Y402H located SCR7 both and H-like 1 (FHL-1), splice (containing SCR1−7) unique biochemical properties. Because known to bind heparin, C-reactive (CRP), M from Streptococcus pyogenes, it has been hypothesized that AMD-associated polymorphism may affect interactions these ligands. In this study, we tested hypothesis context full-length (SCR1−20) FHL-1. We systematically analyzed Y402 H402 variants FHL-1 CRP, several bacterial ligands: M6 PspC pneumoniea, BbCRASP-1 Borrelia burgdorferi. comparing Y FHL-1, found no difference their secretion, cofactor activity, or BbCRASP-1, PspC, but binding CRP protein. This study reveals fundamental properties lays groundwork for elucidating role pathogenesis.