Scientists working at SSRL have found a potential drug target for Type-2 diabetes research.

Type-2 diabetes, associated with rising obesity levels, is predicted to reach epidemic proportions in the next several decades.

Treatment for type-2 diabetes often includes pioglitazone, which has been thought to target the nuclear transcription factor PPARg. Recently, scientists led by Patricia Jennings at the University of California, San Diego determined the molecular structure of another pioglitazone target molecule, mitoNEET, an outer mitochondrial membrane protein.

Using SSRL beamline 9-2 for macromolecular crystallography experiments to determine the three-dimensional protein structure, the team found that mitoNEET has a unique homodimer structure in which two iron-sulfur clusters are bound close together. The two-iron--two-sulfur clusters are approximately 16 Å apart.

When pioglitazone was added, mitoNEET's stability increased tenfold. The study's authors predict that the iron-sulfur binding area may sit close to the outer mitochondrial membrane, where it could receive and transfer clusters that have crossed the membrane.

Paddock, M. L., Wiley, S. E., Axelrod, H. L., Cohen, A. E., Roy, M., Abresch, E. C., Capraro, D., Murphy, A. N., Nechushtai, R., Dixon, J. E. and Jennings, P. A. (2007) MitoNEET is a uniquely folded 2Fe-2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci USA 104, 14342-14347.

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