Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation

Figure 5

Docking of human FXN-1, FXN-2, and FXN-3 on the human tetrameric NFS1/ISCU complex. (a) The human iron-sulfur assembly complex was modeled adopting the E. coli counterpart as a template (PDB code: 3LVL). The NFS1/ISCU complex includes two copies of ISCU (surface representation in purple) and two copies of NFS1 (surface in cyan and yellow, resp.). The backbone of the three frataxin isoforms is depicted in blue (FXN-1), in green (FXN-2), and in red (FXN-3). The three backbones overlap with a pairwise root mean square deviation (RSMD) of about 1.3 Å. (b) Important residues essential for functional interaction are conserved in all isoforms and highlighted in black. Relevant interactions on the complex are highlighted in orange. Basic residues of NFS1 involved in the interaction with the anionic patch of frataxin (R218, R219, R221, and R223) are colored in light green. (c) Zooming on conserved residues among human frataxins was experimentally proven in yeast and humans to play a critical role in the interaction with the ISCU complex: W155 N146 and R165 (R161 in FXN-2 and FXN-3).