The molecular and structural bases for the association of complement C3 mutations with atypical hemolytic uremic syndrome.

ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) associates with complement dysregulation caused by mutations and polymorphisms in complement activators and regulators. However, the reasons why some mutations in complement proteins predispose to aHUS are poorly understood. Here, we have investigated the functional consequences of three aHUS-associated mutations in C3, R592W, R161W and I1157T. First, we provide evidence that penetrance and disease severity for these mutations is modulated by inheritance of documented "risk" haplotypes as has been observed with mutations in other complement genes. Next, we show that all three mutations markedly reduce the efficiency of factor I-mediated C3b cleavage when catalyzed by membrane cofactor protein (MCP), but not when catalyzed by factor H. Biacore analy

SUBMITTER: Martinez-Barricarte R 

PROVIDER: S-EPMC4503813 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature