DYNAMICS OF THE CHAPERONIN ATPASE CYCLE - IMPLICATIONS FOR FACILITATED PROTEIN-FOLDING

The Escherichia coli chaperonins GroEL and GroES facilitate protein fo lding in an adenosine triphosphate (ATP)-dependent manner. After a sin gle cycle of ATP hydrolysis by the adenosine triphosphatase (ATPase) a ctivity of GroEL, the bi-toroidal GroEL formed a stable asymmetric ter nary complex with GroES and nucleotide (bulletlike structures). With e ach subsequent turnover, ATP was hydrolyzed by one ring of GroEL in a quantized manner, completely releasing the adenosine diphosphate and G roES that were tightly bound to the other ring as a result of the prev ious turnover. The catalytic cycle involved formation of a symmetric c omplex (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 prot ein between toroids of high and low affinity. A unifying model for cha peronin-facilitated protein folding based on successive rounds of bind ing and release, and partitioning between committed and kinetically tr apped intermediates, is proposed.