title: The cotranslational function of ribosome-associated Hsp70 in eukaryotic protein homeostasis.
abstract: In eukaryotic cells a molecular chaperone network associates with translating ribosomes, assisting the maturation of emerging nascent polypeptides. Hsp70 is perhaps the major eukaryotic ribosome-associated chaperone and the first reported to bind cotranslationally to nascent chains. However, little is known about the underlying principles and function of this interaction. Here, we use a sensitive and global approach to define the cotranslational substrate specificity of the yeast Hsp70 SSB. We find that SSB binds to a subset of nascent polypeptides whose intrinsic properties and slow translation rates hinder efficient cotranslational folding. The SSB-ribosome cycle and substrate recognition is modulated by its ribosome-bound cochaperone, RAC. Deletion of SSB leads to widespread aggregation of newly synthesized polypeptides. Thus, cotranslationally acting Hsp70 meets the challenge of folding the eukaryotic proteome by stabilizing its longer, more slowly translated, and aggregation-prone nascent polypeptides.
authors: Department of Biology and BioX Program, Stanford University, Stanford, CA 94305-5430, USA.
authors: Felix
authors: F
authors: Willmund
authors: Marta
authors: M
authors: del Alamo
authors: Sebastian
authors: S
authors: Pechmann
authors: Taotao
authors: T
authors: Chen
authors: Véronique
authors: V
authors: Albanèse
authors: Eric B
authors: EB
authors: Dammer
authors: Junmin
authors: J
authors: Peng
authors: Judith
authors: J
authors: Frydman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D017510:Protein Folding; D012270:Ribosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C095192:SSB1 protein, S cerevisiae; C494656:SSE1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C494470:SSB2 protein, S cerevisiae