title: Compartmentation of protein folding in vivo: sequestration of non-native polypeptide by the chaperonin-GimC system.
abstract: The functional coupling of protein synthesis and chaperone-assisted folding in vivo has remained largely unexplored. Here we have analysed the chaperonin-dependent folding pathway of actin in yeast. Remarkably, overexpression of a heterologous chaperonin which traps non-native polypeptides does not interfere with protein folding in the cytosol, indicating a high-level organization of folding reactions. Newly synthesized actin avoids the chaperonin trap and is effectively channelled from the ribosome to the endogenous chaperonin TRiC. Efficient actin folding on TRiC is critically dependent on the hetero-oligomeric co-chaperone GimC. By interacting with folding intermediates and with TRiC, GimC accelerates actin folding at least 5-fold and prevents the premature release of non-native protein from TRiC. We propose that TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. This compartment sequesters newly synthesized actin and other aggregation-sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.
authors.affiliation: The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Glasgow G61 1BD, UK.
authors.forename: K
authors.initials: K
authors.lastname: Siegers
authors.forename: T
authors.initials: T
authors.lastname: Waldmann
authors.forename: M R
authors.initials: MR
authors.lastname: Leroux
authors.forename: K
authors.initials: K
authors.lastname: Grein
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: E
authors.initials: E
authors.lastname: Schiebel
authors.forename: F U
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002451:Cell Compartmentation; D018834:Chaperonin 60 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018833:Chaperonins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008297:Male; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D000199:Actins; D018834:Chaperonin 60; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases; D018833:Chaperonins