Symmetric GroEL:GroES ₂ complexes are the protein-folding functional form of the chaperonin nanomachine

Significance The canonical mechanism of GroEL/GroES protein folding rests on at least three untested assumptions: ( i ) symmetric GroEL-GroES 2 “football” particles have no role; ( ii ) because of negative cooperativity, ATP binds to GroEL, one ring at a time; and ( iii ) the turnover of the chaperonin system occurs at the same rate in the presence of substrate protein (SP) as in its absence. Each of these assumptions is shown to be incorrect. ( i ) Because of an SP-induced change in the kinetic mechanism, the predominant species under protein folding conditions is the symmetric football; ( ii ) simultaneous occupancy of both GroEL rings by ATP and GroES occurs; and ( iii ) the residence time of encapsulated SP is much shorter than believed.