9I1A

Iron loaded human mitochondrial ferritin 20 minute oxygen soak

Summary for 9I1A

• Entry DOI: 10.2210/pdb9i1a/pdb
• Descriptor: Ferritin, mitochondrial, FE (III) ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: iron, ferritin, mitochondria, human, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 21548.57

Authors

Bugg, Z.,Hemmings, A.M.,Bradley, J.M. (deposition date: 2025-01-16, release date: 2026-01-28, Last modification date: 2026-08-12)

Primary citation

Bugg, Z.,Hazlewood, C.,Hemmings, A.M.,Bradley, J.M.,Le Brun, N.E.
Impact of the three-fold channel substitution D131N on kinetics of translocation of Fe 2+ across the protein coat is more severe for human cytosolic H-chain ferritin than for human mitochondrial ferritin.
Dalton Trans, 55:6844-6853, 2026

PubMed Abstract: Ferritins play a key role in iron management in organisms from all kingdoms of life. Excess iron is sequestered in mineral form within the hollow protein shell and can be liberated when supply becomes restricted. The protein consists of 24 isostructural monomeric units that pack with 4-, 3-, and 2-fold symmetry. Channels through the protein coat at the 3-fold axes of ferritins localised in the cytosol of animal cells contain a strictly conserved LCDFXEX 'twin carboxylate' motif, and have been shown to be the major iron entry route to animal ferritins, facilitating access to the H-chain intra-subunit catalytic ferroxidase centre. In the ferritin localised to the mitochondria of animals, there is natural variation within the residues lining this channel, such that the Asp residue of the twin carboxylate motif (Asp131) is not strictly conserved. Here we report X-ray crystallographic and solution kinetic studies of the properties of D131N variants of H-chain and mitochondrial ferritins. X-ray structures revealed significant perturbation of metal binding at the three-fold channels and ferroxidase centres of H-chain ferritin, but a relatively minor effect on mitochondrial ferritin. Likewise, kinetic data showed that rapid Fe uptake was abolished in the D131N variant of H-chain ferritin, but less severely impacted in the equivalent variant of mitochondrial ferritin. Differences were also observed in rates of mineralisation and extent of iron release in the D131N variants of the two ferritins. The implications for the physiological role of mitochondrial cytosolic ferritin are discussed.

PubMed: 41995066
DOI: 10.1039/d5dt02739j

Experimental method

X-RAY DIFFRACTION (1.73 Å)