Inferring Methionine Sulfoxidation and serine Phosphorylation crosstalk from Phylogenetic analyses.

摘要: The sulfoxidation of methionine residues within the phosphorylation motif protein kinase substrates, may provide a mechanism to couple oxidative signals changes in phosphorylation. Herein, we hypothesize that if pair phosphorylatable-sulfoxidable sites are functionally linked, then they might have been coevolving. To test this hypothesis number site pairs previously detected on human stress-related proteins has subjected analysis using eukaryote ortholog sequences and phylogenetic approach. Overall, results support conclusion eIF2α protein, serine at position 218 oxidation 222, belong same functional network. First, observed data were much better fitted by Markovian models assumed coevolution both sites, with respect their counterparts assuming independent evolution (p-value = 0.003). Second, was robust methods used reconstruct relationship between 233 eukaryotic species analyzed. Third, co-distribution phosphorylatable sulfoxidable these positions showed multiple origins throughout eukaryotes, which further supports view an adaptive value for co-occurrence. Fourth, possibility two be due structure-driven compensatory mutations evaluated. suggested factors other than those merely structural behind coevolution. Finally, modifiable from ataxin-2 (S814-M815), ataxin-2-like (S211-M215) Pumilio homolog 1 (S124-M125), reinforce role phosphorylation-sulfoxidation crosstalk. For four analyzed herein, respective PTM (phosphorylatable methionine) found evolving correlated fashion, suggests relevant crosstalk control translation under stress conditions.