Figure 6

Scheme of conformational fluctuations of human Frataxin. FXN folds through an intermediate state (I) with low compactness and ~60% of native secondary structure. Our working hypothesis states that there exist at least two native substates: a closed conformation (C), in which the CTR residues are hidden, and an open conformation (O), in which the CTR possesses a higher solvent accessible surface area and may react to produce the labeled protein (L). Both the closed and the open conformations are native forms of the protein, different from the intermediate and unfolded (U) state. However, the same as the open conformation, the intermediate state—which has an unstructured C terminal¹⁸—and the unfolded state may react with the probes. The open native state may turn to the intermediate and unfolded states. Besides, the closed native state may directly turn to the intermediate (dashed arrow).