9EQ9

Iron loaded mitochondrial ferritin, anaerobic

Summary for 9EQ9

• Entry DOI: 10.2210/pdb9eq9/pdb
• Descriptor: Ferritin, mitochondrial, FE (III) ION, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: ferritin, mitochondrial, iron, human, metal binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 20963.58

Authors

Bugg, Z.,Bradley, J.M.,Le Brun, N.E.,Hemmings, A.M. (deposition date: 2024-03-21, release date: 2025-04-16, Last modification date: 2025-10-29)

Primary citation

Bradley, J.M.,Bugg, Z.,Moore, G.R.,Hemmings, A.M.,Le Brun, N.E.
Observation of the Assembly of the Nascent Mineral Core at the Nucleation Site of Human Mitochondrial Ferritin.
J.Am.Chem.Soc., 147:13699-13710, 2025

PubMed Abstract: Ferritins play a crucial role in iron homeostasis and detoxification in organisms from all kingdoms of life. They are composed of 24 α-helical subunits arranged around an interior cavity where an iron-containing mineral core can be reversibly stored. Despite decades of study, leading to significant progress in defining the routes of Fe uptake and the mechanism of its subsequent oxidation to Fe at diiron catalytic sites termed ferroxidase centers, the process of core synthesis from the product of ferroxidase center activity remains poorly understood. In large part, this is due to the lack of high-resolution structural data on ferritin cores anchored to their nucleation sites on the inner surface of the protein. Mitochondrial ferritins are atypical of those found in higher eukaryotes in that they are homopolymers in which all subunits contain both a ferroxidase center and a presumed but undefined core nucleation site. Here, in conjunction with a novel method for producing iron-enriched ferritin crystals, we exploit these unusual features to structurally characterize both the nucleation site of mitochondrial ferritin and a pentanuclear, ferrihydrite-like iron-oxo cluster formed there. Kinetic data for wild-type and variant proteins confirmed the functional importance of this site, indicating a critical role for E61 in the transfer of Fe from the ferroxidase center to the nascent mineral core.

PubMed: 40223208
DOI: 10.1021/jacs.5c01337

Experimental method

X-RAY DIFFRACTION (1.84 Å)