ROLE OF H-SUBUNIT AND L-SUBUNIT IN MOUSE FERRITIN

Ferritin is an iron-binding protein composed of two subunits, H and L. Tuenty-four of these subunits assemble to form apoferritins whose sub unit composition varies in a characteristic way in different tissues, Using recombinant proteins, we have assessed the role of H and L subun its in mouse ferritin function and compared these to human ferritin su bunits, We report that mouse ferritin subunits exhibit considerable fu nctional 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 ar e 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 substanti al functional differences; murine ferritin H showed a consistent reduc tion 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.