title: Conversion of a chaperonin GroEL-independent protein into an obligate substrate.
abstract: Chaperones assist protein folding by preventing unproductive protein aggregation in the cell. In Escherichia coli, chaperonin GroEL/GroES (GroE) is the only indispensable chaperone and is absolutely required for the de novo folding of at least ∼60 proteins. We previously found that several orthologs of the obligate GroE substrates in Ureaplasma urealyticum, which lacks the groE gene in the genome, are E. coli GroE-independent folders, despite their significant sequence identities. Here, we investigated the key features that define the GroE dependence. Chimera or random mutagenesis analyses revealed that independent multiple point mutations, and even single mutations, were sufficient to confer GroE dependence on the Ureaplasma MetK. Strikingly, the GroE dependence was well correlated with the propensity to form protein aggregates during folding. The results reveal the delicate balance between GroE dependence and independence. The function of GroE to buffering the aggregation-prone mutations plays a role in maintaining higher genetic diversity of proteins.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-56, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501 and.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-56, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501 and.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Niwa
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-56, 4259 Nagatsuta, Midori-ku, Yokohama 226-8501 and. Electronic address: taguchi@bio.titech.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Taguchi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018834:Chaperonin 60 / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D008027:Light; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020543:Proteome; D012542:Scattering, Radiation; D017386:Sequence Homology, Amino Acid; D014509:Ureaplasma / Q000201:enzymology
chemical_list: D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D020543:Proteome; C519385:MetK protein, E coli; D008716:Methionine Adenosyltransferase
keywords: Chaperone; Chaperonin; GroEL; Protein Aggregation; Protein Evolution; Protein Folding; Protein Misfolding