9e8s | pdb_00009e8s
Structure of thioferritin (PfDPSL) with ferrihydrite growth at a single three-fold pore.
Structural highlights
FunctionDPS_PYRFU Protects DNA from oxidative damage by sequestering intracellular Fe(2+) ion and storing it in the form of Fe(3+) oxyhydroxide mineral. One hydrogen peroxide oxidizes two Fe(2+) ions, which prevents hydroxyl radical production by the Fenton reaction (By similarity). It efficiently oxidizes Fe(2+) in the presence of hydrogen peroxide and stores it. Publication Abstract from PubMedIron 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 A structure in the unmineralized state, as well as a 1.91 A 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 A 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. The Mechanism of Mineral Nucleation and Growth in a Mini-Ferritin.,Gauvin CC, Tokmina-Lukaszewska M, Waghwani HK, McBee SC, Douglas T, Bothner B, Lawrence CM J Am Chem Soc. 2025 Oct 15;147(41):37030-37044. doi: 10.1021/jacs.5c05464. Epub , 2025 Oct 6. PMID:41052476[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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