Systems analyses reveal two chaperone networks with distinct functions in eukaryotic cells.
Molecular chaperones assist the folding of newly translated and stress-denatured proteins. In prokaryotes, overlapping sets of chaperones mediate both processes. In contrast, we find that eukaryotes evolved distinct chaperone networks to carry out these functions. Genomic and functional analyses indicate that in addition to stress-inducible chaperones that protect the cellular proteome from stress, eukaryotes contain a stress-repressed chaperone network that is dedicated to protein biogenesis. These stress-repressed chaperones are transcriptionally, functionally, and physically linked to the translational apparatus and associate with nascent polypeptides emerging from the ribosome. Consistent with a function in de novo protein folding, impairment of the translation-linked chaperone network renders cells sensitive to misfolding in the context of protein synthesis but not in the context of environmental stress. The emergence of a translation-linked chaperone network likely underlies the elaborate cotranslational folding process necessary for the evolution of larger multidomain proteins characteristic of eukaryotic cells.
Albanèse
Véronique
V
Department of Biological Sciences and BioX Program, Stanford University, Stanford, CA 94305, USA.
Yam
Alice Yen-Wen
AY
Baughman
Joshua
J
Parnot
Charles
C
Frydman
Judith
J
D000251:Adenosine Triphosphatases; D003600:Cytosol / Q000737:chemistry / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D018832:Molecular Chaperones / Q000145:classification* / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D017510:Protein Folding; D012270:Ribosomes / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D012680:Sensitivity and Specificity; D049490:Systems Biology / Q000379:methods; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C095192:SSB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C494470:SSB2 protein, S cerevisiae