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

Here, we apply our method to predict redox-sensitive disordered regions on a large scale. We analyze the occurrence of these segments in known structures, and connect them to structural and functional features. In order to explore evolutionary trends of redox-sensitive conditionally disordered regions, we estimate their abundance at the proteome level and analyze their enrichment in terms of domains and biological processes. By taking advantage of recent mass spectrometry-based techniques applied to the exploration of redox-sensitive thiols, we can highlight proteins that are likely to use disorder-to-order transition to respond to redox changes in biological settings. We have used experimentally derived datasets generated by two different redox probes: either ICAT (used in the OxICAT redox proteomic method) [16] or biotin-HPDP [15] . Finally, by analyzing disease data, we collected examples of genetic mutations that alter the behaviour of putative redox-sensitive regions.