Dynamics of the chaperonin ATPase cycle: implications for facilitated protein folding.
The Escherichia coli chaperonins GroEL and GroES facilitate protein folding in an adenosine triphosphate (ATP)-dependent manner. After a single cycle of ATP hydrolysis by the adenosine triphosphatase (ATPase) activity of GroEL, the bi-toroidal GroEL formed a stable asymmetric ternary complex with GroES and nucleotide (bulletlike structures). With each subsequent turnover, ATP was hydrolyzed by one ring of GroEL in a quantized manner, completely releasing the adenosine diphosphate and GroES that were tightly bound to the other ring as a result of the previous turnover. The catalytic cycle involved formation of a symmetric complex (football-like structures) as an intermediate that accumulated before the rate-determining hydrolytic step. After one to two cycles, most of the substrate protein dissociated still in a nonnative state, which is consistent with intermolecular transfer of the substrate protein between toroids of high and low affinity. A unifying model for chaperonin-facilitated protein folding based on successive rounds of binding and release, and partitioning between committed and kinetically trapped intermediates, is proposed.
Todd
M J
MJ
E. I. DuPont de Nemours and Company, Central Research and Development Department, Wilmington, DE 19880.
Viitanen
P V
PV
Lorimer
G H
GH
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D018835:Chaperonin 10; D018834:Chaperonin 60; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D017510:Protein Folding; D012273:Ribulose-Bisphosphate Carboxylase / Q000378:metabolism
D001426:Bacterial Proteins; D018835:Chaperonin 10; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D000251:Adenosine Triphosphatases; D012273:Ribulose-Bisphosphate Carboxylase