title: GroEL/ES chaperonin modulates the mechanism and accelerates the rate of TIM-barrel domain folding.
abstract: The GroEL/ES chaperonin system functions as a protein folding cage. Many obligate substrates of GroEL share the (βα)8 TIM-barrel fold, but how the chaperonin promotes folding of these proteins is not known. Here, we analyzed the folding of DapA at peptide resolution using hydrogen/deuterium exchange and mass spectrometry. During spontaneous folding, all elements of the DapA TIM barrel acquire structure simultaneously in a process associated with a long search time. In contrast, GroEL/ES accelerates folding more than 30-fold by catalyzing segmental structure formation in the TIM barrel. Segmental structure formation is also observed during the fast spontaneous folding of a structural homolog of DapA from a bacterium that lacks GroEL/ES. Thus, chaperonin independence correlates with folding properties otherwise enforced by protein confinement in the GroEL/ES cage. We suggest that folding catalysis by GroEL/ES is required by a set of proteins to reach native state at a biologically relevant timescale, avoiding aggregation or degradation.
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Georgescauld
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Popova
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
authors.forename: Amit J
authors.initials: AJ
authors.lastname: Gupta
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bracher
authors.affiliation: Department of Chemistry & Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston MA 02115-5000, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
authors.forename: Manajit
authors.initials: M
authors.lastname: Hayer-Hartl
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.|Munich Center for Integrated Protein Science (CiPSM), Ludwig-Maximilians-Universität München, Butenandtstrasse 13, 81377 Munich, Germany.
authors.forename: F Ulrich
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D018835:Chaperonin 10 / Q000378:metabolism*; D018834:Chaperonin 60 / Q000378:metabolism*; D041961:Deuterium Exchange Measurement; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D045805:Mycoplasma synoviae / Q000201:enzymology / Q000378:metabolism; D007652:Oxo-Acid-Lyases / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase