4DE6

Horse spleen apo-ferritin complex with arachidonic acid

Summary for 4DE6

• Entry DOI: 10.2210/pdb4de6/pdb
• Related: 1XZ1 1XZ3 3F32
• Descriptor: Ferritin light chain, ARACHIDONIC ACID, CADMIUM ION, ... (5 entities in total)
• Functional Keywords: four helix bundle, transport protein
• Biological source: Equus caballus (domestic horse,equine)
• Total number of polymer chains: 1
• Total formula weight: 21397.07

Authors

Bu, W.,Liu, R.,Dmochowski, I.J.,Loll, P.J.,Eckenhoff, R.G. (deposition date: 2012-01-19, release date: 2012-03-07, Last modification date: 2023-09-13)

Primary citation

Bu, W.,Liu, R.,Cheung-Lau, J.C.,Dmochowski, I.J.,Loll, P.J.,Eckenhoff, R.G.
Ferritin couples iron and fatty acid metabolism.
Faseb J., 26:2394-2400, 2012

PubMed Abstract: A physiological relationship between iron, oxidative injury, and fatty acid metabolism exists, but transduction mechanisms are unclear. We propose that the iron storage protein ferritin contains fatty acid binding sites whose occupancy modulates iron uptake and release. Using isothermal microcalorimetry, we found that arachidonic acid binds ferritin specifically and with 60 μM affinity. Arachidonate binding by ferritin enhanced iron mineralization, decreased iron release, and protected the fatty acid from oxidation. Cocrystals of arachidonic acid and horse spleen apoferritin diffracted to 2.18 Å and revealed specific binding to the 2-fold intersubunit pocket. This pocket shields most of the fatty acid and its double bonds from solvent but allows the arachidonate tail to project well into the ferrihydrite mineralization site on the ferritin L-subunit, a structural feature that we implicate in the effects on mineralization by demonstrating that the much shorter saturated fatty acid, caprylate, has no significant effects on mineralization. These combined effects of arachidonate binding by ferritin are expected to lower both intracellular free iron and free arachidonate, thereby providing a previously unrecognized mechanism for limiting lipid peroxidation, free radical damage, and proinflammatory cascades during times of cellular stress.

PubMed: 22362897
DOI: 10.1096/fj.11-198853

Experimental method

X-RAY DIFFRACTION (2.18 Å)