title: Role of H and L subunits in mouse ferritin.
abstract: Ferritin is an iron-binding protein composed of two subunits, H and L. Twenty-four of these subunits assemble to form apoferritins whose subunit composition varies in a characteristic way in different tissues. Using recombinant proteins, we have assessed the role of H and L subunits in mouse ferritin function and compared these to human ferritin subunits. We report that mouse ferritin subunits exhibit considerable functional similarity to their human counterparts, including a prominent role of the H subunit in the facilitation of rapid iron uptake, and a key role of amino acid residues Glu-62 and His-65 in this process. In addition, amino acid residues important to assembly of the protein are conserved between mouse and human, permitting the formation of fully functional hybrid proteins containing both mouse and human subunits. However, murine and human ferritin H subunits also evidenced substantial functional differences; murine ferritin H showed a consistent reduction in iron uptake activity relative to human ferritin H. Creation of chimeric human/mouse ferritin H subunits by "helix swapping" mapped the domain of the protein critical to this activity difference to the DE helix. These findings suggest a novel functional role for carboxyl-terminal domains of the ferritin H subunit.
authors.affiliation: Department of Cancer Biology, Bowman Gray School of Medicine and the Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina 27157, USA.
authors.forename: P
authors.initials: P
authors.lastname: Rucker
authors.forename: F M
authors.initials: FM
authors.lastname: Torti
authors.forename: S V
authors.initials: SV
authors.lastname: Torti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002499:Centrifugation, Density Gradient; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D007501:Iron / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D005293:Ferritins; D007501:Iron