title: Repetitive protein unfolding by the trans ring of the GroEL-GroES chaperonin complex stimulates folding.
abstract: A key constraint on the growth of most organisms is the slow and inefficient folding of many essential proteins. To deal with this problem, several diverse families of protein folding machines, known collectively as molecular chaperones, developed early in evolutionary history. The functional role and operational steps of these remarkably complex nanomachines remain subjects of active debate. Here we present evidence that, for the GroEL-GroES chaperonin system, the non-native substrate protein enters the folding cycle on the trans ring of the double-ring GroEL-ATP-GroES complex rather than the ADP-bound complex. The properties of this ATP complex are designed to ensure that non-native substrate protein binds first, followed by ATP and finally GroES. This binding order ensures efficient occupancy of the open GroEL ring and allows for disruption of misfolded structures through two phases of multiaxis unfolding. In this model, repeated cycles of partial unfolding, followed by confinement within the GroEL-GroES chamber, provide the most effective overall mechanism for facilitating the folding of the most stringently dependent GroEL substrate proteins.
authors.affiliation: From the Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, Zhejiang 314006, China.
authors.forename: Zong
authors.initials: Z
authors.lastname: Lin
authors.forename: Jason
authors.initials: J
authors.lastname: Puchalla
authors.forename: Daniel
authors.initials: D
authors.lastname: Shoup
authors.forename: Hays S
authors.initials: HS
authors.lastname: Rye
mesh_terms: D018835:Chaperonin 10 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D012247:Rhodospirillum rubrum / Q000201:enzymology* / Q000235:genetics; D012273:Ribulose-Bisphosphate Carboxylase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; D012273:Ribulose-Bisphosphate Carboxylase
keywords: Chaperone Chaperonin; GroEL; Hsp60; Molecular Chaperone; Protein Dynamics; Protein Folding; Protein Misfolding
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