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 predicted redox-sensitive structural switches were associated with several biological processes and functions, many of which have already been linked to changes in redox state. One important group includes transcription factors, many of which contain zinc finger domains [84] . In yeast, it has been shown that modulation of the redox status induces reversible changes in the translational machinery and controls protein synthesis [40] . Examples of redoxregulated proteins that rely on conditional disorder are involved in mitochondrial transport and assembly. In mammalians, redox signaling via alteration of redox status of specific protein thiols has been recognized as a major contributor to diverse key processes, such as stem cell proliferation [85] , vertebrate embryonic development [86] , neuronal development [87] , and blood coagulation [88] . Redox regulation is also an emerging theme in cell-cell and cell-ECM interactions [89] , tying together integrin signaling, angiogenesis, and various diseases. All of these processes are present only in higher order eukaryotes, and the heavy involvement of redox-sensitive conditionally disordered proteins is in line with the evolutionary trends identified ( Figure 3 ).