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

As the identified human redox-sensitive proteins fulfill central biological roles, their modulation by mutations is expected to have serious physiological consequences. We used the Humsavar dataset of disease associated germline mutations collected in Uniprot [49] to assess human pathogenic conditions associated with the perturbation of redox-sensitive conditionally disordered regions. We collected disease mutations that either eliminate or introduce cysteine residues in the sequence. In general, cysteine is one of the least common amino acids in proteins. Accordingly, the frequency of cysteine residue in sequences with diseases mutations is only 2.44%. However, its frequency among mutated residues is 6.85%, which places it as the second most mutation-prone residue (after arginine) in the disease dataset. We analyzed these cases to establish a link between the induced structural changes, protein function, and phenotypic alterations.