2g7i
From Proteopedia
Structure of Human Complement Factor H Carboxyl Terminal Domains 19-20: a Basis for Atypical Hemolytic Uremic Syndrome
Overview
Factor H (FH) is the key regulator of the alternative pathway of complement. The carboxyl-terminal domains 19-20 of FH interact with the major opsonin C3b, glycosaminoglycans, and endothelial cells. Mutations within this area are associated with atypical haemolytic uremic syndrome (aHUS), a disease characterized by damage to endothelial cells, erythrocytes, and kidney glomeruli. The structure of recombinant FH19-20, solved at 1.8 A by X-ray crystallography, reveals that the short consensus repeat domain 20 contains, unusually, a short alpha-helix, and a patch of basic residues at its base. Most aHUS-associated mutations either destabilize the structure or cluster in a unique region on the surface of FH20. This region is close to, but distinct from, the primary heparin-binding patch of basic residues. By mutating five residues in this region, we show that it is involved, not in heparin, but in C3b binding. Therefore, the majority of the aHUS-associated mutations on the surface of FH19-20 interfere with the interaction between FH and C3b. This obviously leads to impaired control of complement attack on plasma-exposed cell surfaces in aHUS.
About this Structure
2G7I is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome., Jokiranta TS, Jaakola VP, Lehtinen MJ, Parepalo M, Meri S, Goldman A, EMBO J. 2006 Apr 19;25(8):1784-94. Epub 2006 Apr 6. PMID:16601698 Page seeded by OCA on Sun May 4 04:46:50 2008
