Mutant ferritin L-chains that cause neurodegeneration act in a dominant-negative manner to reduce ferritin iron incorporation.

ABSTRACT: Nucleotide insertions that modify the C terminus of ferritin light chain (FTL) cause neurodegenerative movement disorders named neuroferritinopathies, which are inherited with dominant transmission. The disorders are characterized by abnormal brain iron accumulation. Here we describe the biochemical and crystallographic characterization of pathogenic FTL mutant p.Phe167SerfsX26 showing that it is a functional ferritin with an altered conformation of the C terminus. Moreover we analyze functional and stability properties of ferritin heteropolymers made of 20-23 H-chains and 1-4 L-chains with representative pathogenic mutations or the last 10-28 residues truncated. All the heteropolymers containing the pathogenic or truncated mutants had a strongly reduced capacity to incorporate iron, both

SUBMITTER: Luscieti S 

PROVIDER: S-EPMC2852932 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature