SPECIFICITY IN CHAPERONIN-MEDIATED PROTEIN-FOLDING

CHAPERONINS are ubiquitous multisubunit toroidal complexes that aid pr otein folding in an ATP-dependent manner(1-6). Current models of foldi ng by the bacterial chaperonin GroEL depict its role as unfolding and releasing molecules that have misfolded, so that they can return to a potentially productive folding pathway in solution(7,8). Accordingly, a given target polypeptide might require several cycles of binding and ATP-driven release from different chaperonin complexes before reachin g the native state. Surprisingly, cycling of a target protein does not guarantee its folding, and we report here that unfolded beta-actin or alpha-tubulin both form tight complexes when presented to either GroE L or its mitochondrial homologue, and both undergo cycles of release a nd rebinding upon incubation with ATP, but no native protein is produc ed. We conclude that different chaperonins produce distinctive spectra of folding intermediates.