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

Apart from multicellular eukaryotes, several viruses also exhibit high fredox values. In these cases, fredox values correlate with the complexity of the host, with most high fredox value viruses targeting complex eukaryotes, typically vertebrates. This correlation between host complexity and fredox value is also apparent for several unicellular eukaryotic pathogens. Both T. congolense and P. falciparum (the major causes of the sleeping sickness and malaria, respectively) are unicellular eukaryotes, and such their fredox values are expected to be below 10%, similarly to other organisms with comparable complexity and small proteome size. However, their fredox values rather resemble those of their hosts, with fredox=24.4% and 17.9%, respectively ( Figure 3A ). The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/412692 doi: bioRxiv preprint While the fraction of proteins incorporating redox-sensitive intrinsically disordered regions increases with organism complexity, the typical length of such regions is strikingly constant across various domains of life and viruses ( Figure 3B ). The typical region length is approximately 22 residues, and while eukaryotes have a slightly higher average region length, this is primarily a result of the high apparent length of tandem arrays of redox-sensing regions. This indicates that the basic molecular mechanisms behind redox-sensing structural switches are probably uniform across all life, and the emergence of complexity requires a larger number of proteins utilizing such mechanisms.