Ferritin, the major iron-storage protein, normally is found in a variety of isomeric forms (isoferritins). The structural basis of this molecular heterogeneity and its functional significance for human pathophysiology remain controversial and incompletely understood. The proposed research project investigates the molecular structure and cellular localization of ferritin isoforms through the correlated use of biochemical, immunological, and ultrastructural approaches. Emphasis will be given to studying molecular size polymorphism as one of the two major types of ferritin heterogeneity. The results obtained will test the central hypothesis that ferritin size isoforms have different cellular locations and different functional roles in iron metabolism. The investigations will utilize special systems that uniquely permit the bulk isolation and total purification of some isoferritins that are known both to differ structurally and to be related to iron overload; coordinated studies will assay human materials for the presence of analogous types of ferritin heterogeneity. Analytical biochemistry will be used to examine the protein structure of purified isoferritin molecules and their polypeptide subunits. The relationships between these molecular isoforms and the cellular heterogeneity in liver will be investigated by fractionation of liver cell types followed by bulk purification and biochemical definition of the contained ferritins. The structural basis for the heterogeneity of bone marrow ferritin will be examined using modern biochemical analyses. The validity of the heteropolymer model for the protein structure of ferritin will be tested by ultrastructural immunochemistry of single molecules, using subunit-specific monoclonal or polyclonal immunoprobes.
| Santambrogio, P; Massover, W H (1989) Rabbit serum alpha-2-macroglobulin binds to liver ferritin: association causes a heterogeneity of ferritin molecules. Br J Haematol 71:281-90 |
| Santambrogio, P; Massover, W H (1987) Protein heterogeneity in rabbit liver ferritin: two types of molecular dimers. Biochem Biophys Res Commun 148:1363-9 |
