WITHDRAWN:Hydrodynamic Studies of Human AIF-M2 Protein in Solution

Ahead of Print article withdrawn by publisher. Human apoptosis-inducing factor 2 (AIF-M2, also called AMID) is a flavoprotein oxidoreductase that contains modified flavin 6-hydroxy-FAD. Unlike most apparent flavoproteins, AIF-M2 has DNA binding activity that leads to caspase-independent apoptosis. Although the oxidoreductase and DNA-binding activity of AIF-M2 have been confirmed, the relevance of oxidoreductase activity and DNA-binding activity require consideration. In this study, we used hydrodynamic and kinetic methods to investigate the protein conformational state during the execution of oxidoreductase activity and pro-apoptosis (DNA-binding activity). Results indicated that DNA binding to AIF-M2 resulted in a remarkable conformational change in AIF-M2. It was also found that execution of physiological functions (e.g., oxidoreductase and DNA binding activity) of AIF-M2 required a unique conformation in solution. Our data indicate that the presence of pyridine nucleotide prevents the binding of AIF-M2 to DNA. Based on these results, we suggest that the cellular pyridine nucleotide plays an important role at the onset of apoptosis induced by AIF-M2.