Human ribosomal protein and proteasomal subunit suppress cct mutations and reduce alpha-synuclein toxicity in Saccharomyces cerevisiae

CCT (Chaperonin containing T-complex polypeptide), the chaperonin complex in S. cerevisiae, bears striking similarities to human CCT and serves as a model system to study properties of the human chaperonin complex. In this study, we employ temperature-sensitive (ts) mutants of CCT complex in S. cerevisiae to screen a human glioma cDNA library for identifying human proteins, which on overexpression, can rescue mutations in the CCT complex. Among other proteins, we identify a human ribosomal protein, RPS6p and a proteasomal subunit, PSMA6p as suppressors of cct mutations. As compromised protein folding may result in protein aggregation in the cell, we also studied the effect of the suppressors on protein aggregation. Both the genes reduced toxicity due to alpha-synuclein aggregation in a cog6Δ mutant. RPS6 was more potent in suppressing the ts mutations and in reducing alpha-synuclein toxicity. Yeast homologs of RPS6 and PSMA6 showed similar functions, thus confirming cross-species conservation of the identified functions. •A genetic screen identifies PSMA6 and RPS6 as suppressors of chaperonin complex CCT mutations.•The suppressors act in a dosage-dependent manner.•The suppressor activity is shared by the yeast homologs SCL1 and RPS6A.•All the four proteins alleviate toxicity due to protein aggregation.•This serves as a model system to study cross-species conservation of protein function.