Intrinsically disordered signaling proteins: Essential hub players in the control of stress responses in Saccharomyces cerevisiae

Abstract

Cells have developed diverse mechanisms to monitor changes in their surroundings. This allows them to establish effective responses to cope with adverse environments. Some of these mechanisms have been well characterized in the budding yeast Saccharomyces cerevisiae, an excellent experimental model to explore and elucidate some of the strategies selected in eukaryotic organisms to adjust their growth and development in stressful conditions. The relevance of structural disorder in proteins and the impact on their functions has been uncovered for proteins participating in different processes. This is the case of some transcription factors (TFs) and other signaling hub proteins, where intrinsically disordered regions (IDRs) play a critical role in their function. In this work, we present a comprehensive bioinformatic analysis to evaluate the significance of structural disorder in those TFs (170) recognized in S. cerevisiae. Our findings show that 85.2% of these TFs contain at least one IDR, whereas ~30% exhibit a higher disorder level and thus were considered as intrinsically disordered proteins (IDPs). We also found that TFs contain a higher number of IDRs compared to the rest of the yeast proteins, and that intrinsically disordered TFs (IDTFs) have a higher number of protein-protein interactions than those with low structural disorder. The analysis of different stress response pathways showed a high content of structural disorder not only in TFs but also in other signaling proteins. The propensity of yeast proteome to undergo a liquid-liquid phase separation (LLPS) was also analyzed, showing that a significant proportion of IDTFs may undergo this phenomenon. Our analysis is a starting point for future research on the importance of structural disorder in yeast stress responses.

The GET pathway is a major bottleneck for maintaining proteostasis in Saccharomyces cerevisiae

“…However, 24% of the hits were found to be intrinsically disordered using MobiDB ( https://mobidb.bio.unipd.it/ ; a protein is considered significantly disordered if the glutamine/asparagine content is more than 20% with a pWalz cutoff of 73,55) 37 . Previous studies have predicted 7.7% intrinsically disordered proteins in the yeast proteome 38 , indicating that intrinsically disordered proteins were enriched in our screen.…”

“…24% of the proteins was found to contain intrinsically disordered regions. Previous studies have found that around 7.7% of the Saccharomyces cerevisiae proteome has some degree of disorder 38 . Thus there is a bias for intrinsically disordered proteins among foci-forming proteins in the get mutant analyzed.…”

Cell wall-resident PIR proteins show an inverted architecture inNeurospora crassa, but keep their role as wall stabilizers

“…Since protein repeats, characteristic of CWPs, have been associated with intrinsic disorder [61,62], a common way to form intermolecular complexes [63,64] and a necessary asset to secrete CWPs through the cell wall in bacteria [65], intrinsic disorder was assessed in identified PIRs (Table S2). In general, filamentous fungi PIRs (cluster 1B) were more intrinsically disordered (93.03% of total proteins had at least 1 intrinsically disordered region, IDR, longer than 50 amino acids; 99.31 % of total proteins had at least 1 IDR longer than 30 amino acids), than cluster 1A yeasts PIRs (77.6 % of total proteins had at least 1 IDR longer than 50 amino acids; 91.26 % of total proteins had at least 1 IDR longer than 30 amino acids).…”