General Chemistry

Conclusion

Iron is an essential trace element that is used to form molecules in the body, such as hemoglobin.  Ferritin is the protein within the body that stores iron and releases it through channels in a controlled fashion.  The unique structure of ferritin forms a spherical shell in which the iron is "stored" as Fe(III) in a crystalline mineral. Ferritin consists of 24 peptide subunits that form two types of channels where these subunits intersect;  the 3-fold channel is polar and the 4-fold channel is nonpolar. (The residues that line the channels determine the polarity of the channel.) When the Fe(III) in the crystalline mineral is reduced to Fe(II), the iron becomes solvated and ferritin releases the solvated iron, Fe(H2O)62+, through the 3-fold polar channel. Hence, ferritin can control the amount of available iron in the body, preventing iron disorders like anemia and iron overload.

The three-dimensional structure of ferritin is crucial to its function within the body. (In fact, the three-dimensional stucture of any molecule is critical in determining a molecule's properties and function.) Hence, to better understand ferritin's role in the body, we used different types of molecular representations to study ferritin's three-dimensional stucture. Each representation used in this tutorial gives important information about ferritin. However, none of the representations by themselves can tell us everything we need to know about ferritin. Only by recognizing the value and limitations of each type of representation, and using these representations in conjunction with one another and with other information about the molecule, can we begin to understand the complex relationship between the protein's structure and its function.


References:

Berkow, R., ed. "Iron Overload/Hemochromatosis," The Merck Manual, 16th ed., 1992. Reprinted by Thomas, S.; Snyder, D., web authors, The American Hemochromatosis Society, Inc.

Frey, R.; Donlin, M.; Bashkin, J. "Ferritin Molecular-Graphics Tutorial," Washington University: St. Louis, MO, 1995.

Griffith, H. W. "Anemia, Iron-Deficiency," The Complete Guide to Symptoms, Illness & Surgery, The Putnam Berkley Group, Inc., 1995; electronic rights by Medical Data Exchange.

Harrison, P.M., et al. In Iron Transport and Storage; Ponka, P.; Schulman, H.M.; Woodworth, R.C., Eds.; CRC: Boca Raton, FL, 1990; pp 81-101.

Insight II graphical program; Molecular Simulations, Inc. URL: http://www.msi.com.

Lawson, D.M., et al. "Solving the Structure of Human H Ferritin by Genetically Engineering Crystal Contacts," Nature 1991, 349, 541-544. (Ferritin PDB coordinates, Brookhaven Protein Data Bank.)

Modern Life Guide- Body Elements, 1996. URL: http://www.modlife.com/MLG/body.html.

K.L. Taft, et al. "A Mixed-Valent Polyiron Oxo Complex that Models the Biomineralization of the Ferritin Core," Science, 1993, 259, 1302.

Persistence of Vision Ray Tracer (POV-Ray). URL: http://www.povray.org.

Theil, E.C. "Ferritin: Structure, Gene Regulation, and Cellular Function in Animals, Plants, and Microorganisms," Annu. Rev. Biochem. 1987, 56, 289-316.

Stryer, L. In Biochemistry, 4th. ed., W.H. Freeman and Co.: New York, 1995, pp. 18-24.

Vander, A.J.; Sherman, J.H.; Luciano, D.S. In Human Physiology: The Mechanisms of Body Function, 6th ed., Mc-Graw-Hill, Inc.: New York, 1994, p. 398.


Acknowledgements:

The authors thank Bill Buhro for obtaining the structural information for the iron-mineral core, Greg Noelken for creating the Jmol script files, and Dewey Holten, Michelle Gilbertson, Jody Proctor and Carolyn Herman  for many helpful suggestions in the writing of this tutorial.

The development of this tutorial was supported by a grant from the Howard Hughes Medical Institute, through the Undergraduate Biological Sciences Education program, Grant HHMI# 71199-502008 to Washington University.

 


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Revised: 2004-08-08