9E8S

Structure of thioferritin (PfDPSL) with ferrihydrite growth at a single three-fold pore.

Summary for 9E8S

• Entry DOI: 10.2210/pdb9e8s/pdb
• Related: 9CZ0 9CZ8 9CZ9
• EMDB information: 47728
• Descriptor: DNA protection during starvation protein, FE (III) ION, OXYGEN MOLECULE, ... (5 entities in total)
• Functional Keywords: ferritin, thioferritin, oxidative stress, iron homeostasis, iron mineral, ferric oxyhydroxide, mineral core, protein cage, metal binding protein
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 12
• Total formula weight: 259385.28

Authors

Gauvin, C.C.,Waghwani, H.K.,Tokmina-Lukaszewska, M.,Bothner, B.,Douglas, T.,Lawrence, C.M. (deposition date: 2024-11-06, release date: 2025-10-29)

Primary citation

Gauvin, C.C.,Tokmina-Lukaszewska, M.,Waghwani, H.K.,McBee, S.C.,Douglas, T.,Bothner, B.,Lawrence, C.M.
The Mechanism of Mineral Nucleation and Growth in a Mini-Ferritin.
J.Am.Chem.Soc., 147:37030-37044, 2025

PubMed Abstract: Iron is an enigmatic element. While necessary for life, as Fe(II) it also catalyzes formation of reactive oxygen species. To mitigate this, cellular life has evolved the ferritin protein superfamily, which includes the 24 subunit ferritins and bacterioferritins, and 12 subunit mini-ferritins (DPS). Each catalyze the oxidation of Fe(II) to ferric oxyhydroxide, which is then sequestered within the hollow protein shell. While there is a wealth of structural information on unmineralized ferritins, high resolution information on iron loaded ferritins is lacking, and the mechanism of iron mineralization is poorly understood. To address this, we followed iron loading in a mini-ferritin by cryo-EM. We determined a 1.86 Å structure in the unmineralized state, as well as a 1.91 Å structure of an early, iron loading state in which the mini-ferritin catalyzes nucleation of ferric oxyhydroxide at the acidic 3-fold pores. Mechanistically, a conserved crucible of precisely positioned glutamates and unsaturated main chain carbonyls are employed as a template to catalyze nucleation. A 2.4 Å structure at a later time point was also determined, revealing the role of a second constellation of main-chain carbonyls on the interior surface that subsequently supports crystalline mineral growth, that then proceeds into the center of the particle. Notably, the visualized mineral is consistent with one of two competing structural descriptions for ferrihydrite. This study provides the first pseudoatomic level observation of controlled mineral nucleation and growth in any member of the ferritin superfamily, and informs general mechanisms of nucleation and biomineralization.

PubMed: 41052476
DOI: 10.1021/jacs.5c05464

Experimental method

ELECTRON MICROSCOPY (2.48 Å)