| Ferritin light chain (FTL), encoded by the FTL gene on chromosome 19q13.33, is one of two subunits (with ferritin heavy chain, FTH) that self-assemble into a 24-meric hollow spherical nanocage (~450 kDa) serving as the primary intracellular iron storage protein across eukaryotes. Each FTL monomer adopts a compact globular fold with a five α-helical bundle (A-E helices) forming the subunit core; 24 FTL/FTH subunits oligomerize via hydrophobic inter-subunit contacts at 4-fold (ferric iron entry channels) and 3-fold (iron nucleation/release pores) symmetry axes, creating a ~80 Å diameter central cavity lined by acidic residues (Glu, Asp) that nucleate ferrihydrite mineral core formation. Unlike FTH's ferroxidase center, FTL lacks catalytic residues (Glu27, Tyr34, Glu62, Gln141, and Glu107 are absent) but facilitates Fe(III) precipitation through surface phosphate-binding sites and iron channel clusters. FTL promotes long-term iron storage by accelerating ferrihydrite nucleation, detoxifying labile iron pool to prevent Fenton-mediated ROS damage, regulates translationally by iron-responsive element (IRE)/IRP1 binding in its 5' UTR; tissue-specific H/L ratios modulate iron kinetics (L-rich slower release). FTL mutations cause hereditary hyperferritinemia-cataract syndrome (upregulated apo-ferritin), neurodegeneration with brain iron accumulation (NBIA3), and contribute to cancer. |
