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

While disulfide bridges usually from under oxidative conditions, metal binding is more common in reducing environment. Consequently, these structural features are usually complementary and there are only, a few structures contained both cysteine clusters and disulfide bonds. While in certain cases the disulfide bond formation could be a crystallization artefact (e.g.2g45), in many cases, the complementary nature of metal binding and disulfide bond formation can ensure a stable structure under a variety of conditions. As a counterpoint to structures with both of the stabilizing features, a relatively small number of predicted proteins (88, 0.62%) did not have either. The majority of these structures describe heme binding proteins, which rely on heme groups coordinated partially by cysteines for their stability, and might in fact be involved in redox regulation [37] . However, disorder-to-order transitions are not necessarily coupled to redox regulation. In general, examples without the capacity to form either disulfide bonds or cysteine clusters are treated as likely false positives. However, the number of such cases in PDB structures represent less than 1% of all structures in our dataset ( Figure 2A ). The overall relatively low rate of predicted redox-sensitive conditionally disordered regions in known structures and their strong correlation with strongly stabilizing structural features add strong credibility to IUPred2A redox-sensitive predictions.