title: A systematic survey of in vivo obligate chaperonin-dependent substrates.
abstract: Chaperonins are absolutely required for the folding of a subset of proteins in the cell. An earlier proteome-wide analysis of Escherichia coli chaperonin GroEL/GroES (GroE) interactors predicted obligate chaperonin substrates, which were termed Class III substrates. However, the requirement of chaperonins for in vivo folding has not been fully examined. Here, we comprehensively assessed the chaperonin requirement using a conditional GroE expression strain, and concluded that only approximately 60% of Class III substrates are bona fide obligate GroE substrates in vivo. The in vivo obligate substrates, combined with the newly identified obligate substrates, were termed Class IV substrates. Class IV substrates are restricted to proteins with molecular weights that could be encapsulated in the chaperonin cavity, are enriched in alanine/glycine residues, and have a strong structural preference for aggregation-prone folds. Notably, approximately 70% of the Class IV substrates appear to be metabolic enzymes, supporting a hypothetical role of GroE in enzyme evolution.
authors.affiliation: Department of Medical Genome Sciences, University of Tokyo, FSB401, Kashiwa, Chiba, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakahigashi
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Hideki
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000595:Amino Acid Sequence; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D055432:Metabolomics; D017510:Protein Folding; D040901:Proteomics; D013379:Substrate Specificity
chemical_list: D018834:Chaperonin 60; D029968:Escherichia coli Proteins