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 structural/functional consequences of cysteine modifications identified in these experiments can be heterogeneous, and not all of them are expected to induce a transition in the structural state of the affected region. Nevertheless, in several cases, the identified proteins with modified cysteines overlapped with predicted conditionally disordered regions. As these predictions suggest a specific mechanism underlying the redox-sensitivity, we took a closer look at these examples (Table 1 ). In one example, the GAS1 protein is anchored to the plasma membrane and to the cell wall. In addition to the catalytic glucanosyltransferase domain, it also contains a cysteine rich domain. The redox-sensitivity of these cysteines in not easy to explain, as they are required for the normal folding and stability of the protein [41] . An interesting case corresponds to YDJ1, a yeast homolog of the chaperone DnaJ, a zinc containing co-chaperone, involved in mitochondrial protein import. The central cysteine-rich domain, which contains four repeats of the motif CXXCXGXG, is predicted as conditionally disordered. Its redox-sensitivity suggests that it could be involved in oxidative-stress response, similarly to Hsp33. The validity of the prediction is supported by the notion that redox regulation was established for the human homologue of DnaJ [42] .