Iron plays an integral role in many biochemical processes essential for life. Now, working in part at SSRL's Beam Line 9-2, a team of researchers led by Martin Lawrence from Montana State University has solved the structure of a protein critical to the process of importing iron into cells. The results were published in the May 27, 2008 edition of the Proceedings of the National Academy of Sciences.

In humans, iron is predominantly found in hemoglobin, the oxygen carrying component in red blood cells (RBCs). As RBCs mature, they incorporate iron into hemoglobin. A protein called Steap3 plays a crucial role in this process.

The Steap family includes four proteins involved in various crucial processes. Malfunction or overexpression of Steap proteins is associated with a range of diseases, from anemia to prostate cancer. In the current study, the team solved the structure of the oxidoreductase domain of Steap3 responsible for changing the oxidation state of iron from Fe³⁺ to Fe²⁺. This step makes it possible for iron to enter the RBC precursor cells where it can be incorporated into heme, the molecule that gives hemoglobin the capacity for carrying oxygen.

Understanding the unique structure of the oxidoreductase domain of Steap3 could lead to more precisely targeted drugs for treating certain disorders, with fewer side effects. Research is ongoing to understand the overall structures of the other Steap proteins.

The project was carried out in collaboration with Mark D. Fleming from Children's Hospital and Harvard Medical School, Boston.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/steap3.html

Anoop K. Sendamarai, Robert S. Ohgami, Mark D. Fleming, and C. Martin Lawrence (2008). Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle. Proc. Natl. Acad. Sci., 105:7410-7415.