title: ATP-triggered conformational changes delineate substrate-binding and -folding mechanics of the GroEL chaperonin.
abstract: The chaperonin GroEL assists the folding of nascent or stress-denatured polypeptides by actions of binding and encapsulation. ATP binding initiates a series of conformational changes triggering the association of the cochaperonin GroES, followed by further large movements that eject the substrate polypeptide from hydrophobic binding sites into a GroES-capped, hydrophilic folding chamber. We used cryo-electron microscopy, statistical analysis, and flexible fitting to resolve a set of distinct GroEL-ATP conformations that can be ordered into a trajectory of domain rotation and elevation. The initial conformations are likely to be the ones that capture polypeptide substrate. Then the binding domains extend radially to separate from each other but maintain their binding surfaces facing the cavity, potentially exerting mechanical force upon kinetically trapped, misfolded substrates. The extended conformation also provides a potential docking site for GroES, to trigger the final, 100° domain rotation constituting the "power stroke" that ejects substrate into the folding chamber.
authors.affiliation: Crystallography and Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Clare
authors.forename: Daven
authors.initials: D
authors.lastname: Vasishtan
authors.forename: Scott
authors.initials: S
authors.lastname: Stagg
authors.forename: Joel
authors.initials: J
authors.lastname: Quispe
authors.forename: George W
authors.initials: GW
authors.lastname: Farr
authors.forename: Maya
authors.initials: M
authors.lastname: Topf
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Horwich
authors.forename: Helen R
authors.initials: HR
authors.lastname: Saibil
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001419:Bacteria / Q000737:chemistry / Q000378:metabolism; D018835:Chaperonin 10 / Q000378:metabolism; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism; D020285:Cryoelectron Microscopy; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D018835:Chaperonin 10; D018834:Chaperonin 60; D029968:Escherichia coli Proteins; C028715:GroE protein, E coli; D006360:Heat-Shock Proteins; D000255:Adenosine Triphosphate