Structural\nAnalysis of Variants of the Ferritin Light\nChain Protein and Its Relationship with Neuroferritinopathy

Ferritin is a highly conserved spherical protein that\nstores iron\nand possesses triple and quadruple symmetry input ports. Additionally,\nit is composed of light chains that can be affected by post-translational\nmutations, reducing the iron storage capacity in the brain and leading\nto neuroferritinopathy, which is a rare disease with limited bioinformatics\ndata. In this study, we analyzed the biochemical mechanism of different\nferritin mutations reported in the literature, through the characterization\nand determination of the <i>in silico</i> structural model\nby searching databases, implementing bioinformatics programs such\nas Jalview, NetNGlyc 1.0, NetOGlyc 3.1, and three-dimensional structure\npredictors with machine learning such as Alphafold, demonstrating\nthe generation of hairpin and steric hindrances that hinder the aggregation\nof subunits and changes in the size and arrangement of quadruple and\ntriple entry holes of the A96T mutation compared to the wild-type\nprotein, since in the quadruple entry hole, a decrease in area is\nobserved compared to the wild-type protein and the triple entry hole\nhas a decrease in distance measurements of 6.504 Å. This possibly\naffects the functionality of the protein, thus releasing high concentrations\nof iron in the brain and causing neurodegeneration.