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Stability and functionality of HL heteropolymer ferritins responsible for a hereditary ferritinopathy disorder
Author(s) -
McNally Justin,
Arosio Paolo,
Bou-Abdallah Fadi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.581.12
Subject(s) - ferritin , protein subunit , chemistry , mutant , crystallography , biochemistry , gene
Mammalian ferritins typically consist of 24 structurally similar but functionally different subunit types named H and L capable of accommodating up to 4500 Fe atoms per molecule. Heteropolymer ferritins having mutations on the L‐subunit cause hereditary ferritinopathy, a neurodegenerative disease characterized by abnormal accumulation of ferritin and iron in the central nervous system. Here, we characterize three pathogenic L‐ferritin mutants (L154fs, L167fs, and L148fs also known as Ln1, Ln2 and L442P) and one non‐pathogenic variant (L135P) for their iron uptake, oxidation and release properties. Overall, the data show iron loading capacity ranging between 1800–2400 Fe/shell for all HL samples with Ln2 holding the least amount of iron. The order of stability of the HL samples is HL > H‐chain > L135P > Ln2 > Ln1 > L442P. The rates of Fe oxidation were similar in all HL samples with a consistently noticeable higher rate with L442P. The mechanism of Fe oxidation appeared to proceed mainly via a ferroxidation reaction with about ~ 2:1 Fe:O 2 ratio and slowly climbing to ~ 3:1 at higher iron loadings. Ln1 and L442P had a higher rate of Fe mobilization consistent with the onset of neuroferritinopathy. This work is supported by a Kilmer Apprenticeship and a Cottrell College Science Award (ID # 7892) from Research Corporation.