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

Redox-dependent disorder-to-order transitions have been described in detail in only a few cases [6, 7] . For this reason, rigorous benchmarking on a large number of positive and negative data is not possible for the prediction of redox-sensitive structural transitions. Instead, IUPred2A was established and is further customized in this study, to best describe the available experimentally verified examples. The prediction is based on the generation of two prediction profiles, one using the original amino acid sequence (redox_plus, assuming cysteine stabilization) and one with mutating each cysteine to serine (redox_minus, corresponding to the lack of cysteine stabilization). While the prediction scores would differ for any sequences containing cysteines, in most cases, no changes in the overall order-disorder tendency would be observed. Our hypothesis was that in the cases of sequences that undergo disorder-to-order transition upon changes in redox conditions, a pronounced shift could be observed with the redox_plus profile predicted as ordered, and the redox_minus profile predicted as disordered. Redox-sensitive regions involved in this type of transition are predicted based on the observed divergence of the two profiles (See Data and Methods).