title: Substrate protein folds while it is bound to the ATP-independent chaperone Spy.
abstract: Chaperones assist in the folding of many proteins in the cell. Although the most well-studied chaperones use cycles of ATP binding and hydrolysis to assist in protein folding, a number of chaperones have been identified that promote folding in the absence of high-energy cofactors. Precisely how ATP-independent chaperones accomplish this feat is unclear. Here we characterized the kinetic mechanism of substrate folding by the small ATP-independent chaperone Spy from Escherichia coli. Spy rapidly associates with its substrate, immunity protein 7 (Im7), thereby eliminating Im7's potential for aggregation. Remarkably, Spy then allows Im7 to fully fold into its native state while it remains bound to the surface of the chaperone. These results establish a potentially widespread mechanism whereby ATP-independent chaperones assist in protein refolding. They also provide compelling evidence that substrate proteins can fold while being continuously bound to a chaperone.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, and the Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Stull
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, and the Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Koldewey
authors.affiliation: Astbury Centre for Structural and Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Humes
authors.affiliation: Astbury Centre for Structural and Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Radford
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, and the Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: James C A
authors.initials: JCA
authors.lastname: Bardwell
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D007700:Kinetics; D018832:Molecular Chaperones / Q000378:metabolism*; D033903:Periplasmic Proteins / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding
chemical_list: D002352:Carrier Proteins; C509253:E colicin-binding immunity protein Im7, E coli; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D033903:Periplasmic Proteins; C104888:Spy protein, E coli