Chaperonins GroEL and GroES form two types of hetero-oligomers in vitro that can mediate the folding of proteins. Chemical cross-linking and electron microscopy showed that in the presence of adenosine triphosphate (ATP), two GroES(7) rings can successively bind a single GroEL(14) core oligomer. The symmetric GroEL(14)(GroES(7))(2) chaperonin, whose central cavity appears obstructed by two GroES(7) rings, can nonetheless stably bind and assist the ATP-dependent refolding of RuBisCO enzyme. Thus, unfolded proteins first bind and possibly fold on the external envelope of the chaperonin hetero-oligomer.