Mark Paddock, Ph.D University of California, San Diego

MitoNEET, a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs, is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (E_M) could be tuned. We found that the protein could tolerate an array of mutations that modified the E_M of the [2Fe-2S] center over a range of ~700 mV, which is the largest E_M range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to -300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent.