Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

Gábor Erdos; Bálint Mészáros; Dana Reichmann; Zsuzsanna Dosztányi

The number of fully characterized redox-induced folding/unfolding examples are rather limited. However, the developed method can be further characterized and refined using the vast amount of information encoded in protein structures containing either oxidized or reduced forms of cysteines in the PDB. To this end, we collected structures from the PDB using a filtering of 40% sequence identity. The predictions were run using the sequence from the corresponding PDB file. The presence of disulfide bonds was calculated from the atomic coordinates. However, cysteine residues that are involved in coordinating metal ions are also often located in close proximity. Such clusters were also identified based on the coordinates (see Data and Methods). The statistics for each PDB chain in the non-redundant dataset is given in the supplementary material. Redox-sensitive regions were predicted for 711 out of 14,145 structures, representing only 5.02% of cases ( Figure 2A ). Most of the redox-sensitive regions corresponded to structures stabilized by disulfide bridges (417, 2.95 %), or cysteine clusters, coordinating either Zn 2+ , Cu 2+ or Fe 2+ clusters (214, 1.51%). However, 1,566 structures with disulfide bonds and 344 structures with cysteine clusters did not contain predicted redox-sensitive structural switches. In general, structures with redoxsensitive regions had a higher number of disulfide bonds or cysteine clusters ( Figure 2B and 2C).