9bq5
C-terminus truncated (last two residues) mutant of Human light chain ferritin reacted with iron (3 Fe2+ to ferritin monomer ratio). Reconstruction of particles with no nanoparticle.
Structural highlights
DiseaseFRIL_HUMAN Defects in FTL are the cause of hereditary hyperferritinemia-cataract syndrome (HHCS) [MIM:600886. It is an autosomal dominant disease characterized by early-onset bilateral cataract. Affected patients have elevated level of circulating ferritin. HHCS is caused by mutations in the iron responsive element (IRE) of the FTL gene.[1] Defects in FTL are the cause of neurodegeneration with brain iron accumulation type 3 (NBIA3) [MIM:606159; also known as adult-onset basal ganglia disease. It is a movement disorder with heterogeneous presentations starting in the fourth to sixth decade. It is characterized by a variety of neurological signs including parkinsonism, ataxia, corticospinal signs, mild nonprogressive cognitive deficit and episodic psychosis. It is linked with decreased serum ferritin levels.[2] [3] FunctionFRIL_HUMAN Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).[4] [5] Publication Abstract from PubMedVisualizing the structure of the protein-inorganic interface is critically important for a more complete understanding of biomineralization. Unfortunately, there are limited approaches for the direct and detailed study of biomolecules that interact with inorganic materials. Here, we use single-particle cryo-electron microscopy (cryo-EM) to study the protein-nanoparticle (NP) interactions of human light chain ferritin and visualize the high-resolution details of the protein-inorganic interface. In this work, we determined the 2.85 A structure of human light chain ferritin bound to its native iron oxide NP substrate. The resulting cryo-EM maps confirmed and enhanced previously proposed interactions of the protein with the material along the B-helix and revealed new interaction at the C-terminus of light chain ferritin. This work sheds new light on the mechanisms of ferritin biomineralization and further demonstrates the application of cryo-EM for the study of protein-inorganic systems. Observation of the Protein-Inorganic Interface of Ferritin by Cryo-Electron Microscopy.,Sen S, Thaker A, Haymaker A, Williams D, Chiu PL, Nannenga BL J Am Chem Soc. 2025 Jan 29;147(4):3333-3340. doi: 10.1021/jacs.4c13873. Epub 2025 , Jan 15. PMID:39815632[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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