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GroEL and GroES form a chaperonin nano-cage for proteins up to ∼60 kDa to fold in isolation. Here we explored the structural features of the chaperonin cage critical for rapid folding of encapsulated substrates. Modulating the volume of the GroEL central cavity affected folding speed in accordance with confinement theory. Small proteins (∼30 kDa) folded more rapidly as the size of the cage was gradually...