EVIDENCE THAT H-CHAINS AND L-CHAINS HAVE COOPERATIVE ROLES IN THE IRON-UPTAKE MECHANISM OF HUMAN FERRITIN

被引:249
作者
LEVI, S
YEWDALL, SJ
HARRISON, PM
SANTAMBROGIO, P
COZZI, A
ROVIDA, E
ALBERTINI, A
AROSIO, P
机构
[1] UNIV MILAN, SAN RAFFAELE INST, DEPT BIOMED SCI & TECHNOL, VIA OLGETTINA 60, I-20122 MILAN, ITALY
[2] KREBS INST BIOMOLEC RES, DEPT MOLEC BIOL, SHEFFIELD S10 2TN, ENGLAND
[3] UNIV BRESCIA, CATTEDRA CHIM APPLICATA SCI BIOMED, BRESCIA, ITALY
基金
英国惠康基金;
关键词
D O I
10.1042/bj2880591
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The ability to incorporate iron in vitro was studied in homopolymers of human ferritin L-chain, human ferritin H-chain and its variants and in homopolymer mixtures. The H-chain variants carried amino acid substitutions in the ferroxidase centre and/or in carboxy residues on the cavity surface. Iron incorporation was examined by gel electrophoresis of the reaction products by staining for iron and protein. It was found that inactivation of the ferroxidase centre combined with the substitution of four carboxy groups on the cavity abolished the ability of H-chain ferritin to incorporate iron. Competition experiments with limited amounts of iron showed that, at neutral pH, L-chain ferritin is more efficient in forming iron cores than the H-chain variants altered at the ferroxidase activity or in the cavity. Competition experiments at pH 5.5 demonstrated that L-chain apoferritin is able to incorporate iron only when in the presence of H-chain variants with ferroxidase activity. The results indicate that L-chain apoferritin has a higher capacity than the H-chain apoferritin to induce iron-core nucleation, whereas H-chain ferritin is superior in promoting Fe(II) oxidation. The finding of cooperative roles of the H- and L-chains in ferritin iron uptake provides a clue to understanding the biological function of isoferritins.
引用
收藏
页码:591 / 596
页数:6
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