28LZ

Iron loaded human H-chain ferritin, 20 minute oxygen soak

Summary for 28LZ

• Entry DOI: 10.2210/pdb28lz/pdb
• Descriptor: Ferritin heavy chain, FE (III) ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: iron, ferritin, human, h-chain, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 21648.64

Authors

Bugg, Z.,Bradley, J.M.,Le Brun, N.E.,Hemmings, A.M. (deposition date: 2026-02-06, release date: 2026-06-10)

Primary citation

Bugg, Z.,Bradley, J.M.,Hemmings, A.M.,Le Brun, N.E.
Ferritin Iron Mineralisation: Route of Fe 3+ Transfer From the Ferroxidase Centre to the Inner Cavity of Human H-Chain Ferritin.
Angew.Chem.Int.Ed.Engl., :e1203843-e1203843, 2026

PubMed Abstract: Ferritin-catalysed Fe oxidation by reaction with O occurs at an intra-subunit diiron site known as the ferroxidase centre (FoC). Currently, how Fe, the key substrate for iron core nucleation/mineralisation, transfers from the FoC to the inner protein surface/central cavity where the mineral is laid down is unknown. Iron-binding sites that become occupied following exposure of anaerobic, Fe-bound human cytosolic H-chain ferritin (HuHF) to O were identified by time-resolved x-ray crystallography. In addition to the two FoC iron sites, three further sites were identified, each involving Glu61 as a coordinating residue. Substitution by a non-coordinating residue (variant E61A) eliminated binding at these additional iron sites. Solution kinetic studies of Fe oxidation and iron core mineralisation in wild-type HuHF and its E61A variant showed that rapid Fe oxidation was unaffected by loss of Glu61, ruling out an important role for these sites in either guiding Fe to the FoC, or in the mechanism of FoC-catalysed Fe oxidation. Conversely, the transfer of Fe out of the FoC and core mineralisation were both severely affected in the E61A variant. A mechanism for Fe transfer from the FoC to the inner protein surface is proposed.

PubMed: 42216818
DOI: 10.1002/anie.1203843

Experimental method

X-RAY DIFFRACTION (1.94 Å)