Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome.

ABSTRACT: 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 basi

SUBMITTER: Jokiranta TS 

PROVIDER: S-EPMC1440827 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature