Chaperonin function: Folding by forced unfolding

The ability of the GroEL chaperonin to unfold a protein trapped in a misfol ded condition was detected and studied by hydrogen exchange. The GroEL-indu ced unfolding of its substrate protein is only partial, requires the comple te chaperonin system, and is accomplished within the 13 seconds required fo r a single system turnover. The binding of nucleoside triphosphate provides the energy for a single unfolding event; multiple turnovers require adenos ine triphosphate hydrolysis. The substrate protein is released on each turn over even if it has not yet refolded to the native state. These results sug gest that GroEL helps partly folded but blocked proteins to fold by causing them first to partially unfold. The structure of GroEL seems well suited t o generate the nonspecific mechanical stretching force required for forcefu l protein unfolding.