2g7i

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spinqualitylabelsall models 2g7i, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of Human Complement Factor H Carboxyl Terminal Domains 19-20: a Basis for Atypical Hemolytic Uremic Syndrome

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Complement factor H deficiency OMIM:[134370], Factor H and factor H-like 1 OMIM:[134370], Hemolytic-uremic syndrome OMIM:[134370], Macular degeneration, age-related, 4 OMIM:[134370], Membranoproliferative glomerulonephritis with CFH deficiency OMIM:[134370]

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

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